Yves-Henri SANEJOUAND
Directeur de recherche CNRS
section 13
| Équipe : |
Thèmes de recherche
Modélisation des macromolécules biologiques. Lien structure-dynamique-fonction des protéines.
Publications
1 publication
Sanejouand, Yves-Henri
On the unknown proteins of eukaryotic proteomes Article de journal
Dans: Journal of Molecular Evolution, vol. 91, p. 492-501, 2023.
@article{sanejouand2023unknown,
title = {On the unknown proteins of eukaryotic proteomes},
author = {Yves-Henri Sanejouand},
url = {https://doi.org/10.1007/s00239-023-10116-1},
doi = {10.1007/s00239-023-10116-1},
year = {2023},
date = {2023-05-23},
urldate = {2022-09-22},
journal = {Journal of Molecular Evolution},
volume = {91},
pages = {492-501},
abstract = {In order to study unknown proteins on a large scale, a reference system has been set up for the three major eukaryotic lineages, built with 36 proteomes as taxonomically diverse as possible. Proteins from 362 eukaryotic proteomes with no known homologue in this set were then analyzed, focusing noteworthy on singletons, that is, on unknown proteins with no known homologue in their own proteome. Consistently, according to Uniprot, for a given species, no more than 12% of the singletons thus found are known at the protein level. Also, since they rely on the information found in the alignment of homologous sequences, predictions of AlphaFold2 for their tridimensional structure are usually poor. In the case of metazoan species, the number of singletons seems to increase as a function of the evolutionary distance from the reference system. Interestingly, no such trend is found in the cases of viridiplantae and fungi, as if the timescale on which singletons are added to proteomes were different in metazoa and in other eukaryotic kingdoms. In order to confirm this phenomenon, further studies of proteomes closer to those of the reference system are however needed.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In order to study unknown proteins on a large scale, a reference system has been set up for the three major eukaryotic lineages, built with 36 proteomes as taxonomically diverse as possible. Proteins from 362 eukaryotic proteomes with no known homologue in this set were then analyzed, focusing noteworthy on singletons, that is, on unknown proteins with no known homologue in their own proteome. Consistently, according to Uniprot, for a given species, no more than 12% of the singletons thus found are known at the protein level. Also, since they rely on the information found in the alignment of homologous sequences, predictions of AlphaFold2 for their tridimensional structure are usually poor. In the case of metazoan species, the number of singletons seems to increase as a function of the evolutionary distance from the reference system. Interestingly, no such trend is found in the cases of viridiplantae and fungi, as if the timescale on which singletons are added to proteomes were different in metazoa and in other eukaryotic kingdoms. In order to confirm this phenomenon, further studies of proteomes closer to those of the reference system are however needed.
1 publication
Sanejouand, Yves-Henri
At least three xenon binding sites in the glycine binding domain of the N-methyl D-aspartate receptor Article de journal
Dans: Archives of biochemistry and biophysics, vol. 724, p. 109265, 2022, (arXiv: 2203.02219).
@article{sanejouand_at_2022,
title = {At least three xenon binding sites in the glycine binding domain of the N-methyl D-aspartate receptor},
author = {Yves-Henri Sanejouand},
url = {http://arxiv.org/abs/2203.02219},
doi = {https://doi.org/10.1016/j.abb.2022.109265},
year = {2022},
date = {2022-03-01},
urldate = {2022-03-01},
journal = {Archives of biochemistry and biophysics},
volume = {724},
pages = {109265},
abstract = {Xenon can produce general anesthesia. Its main protein target is the N-methyl-D-aspartate receptor, a ionotropic channel playing a pivotal role in the function of the central nervous system. The molecular mechanisms allowing this noble gas to have such a specific effect remain obscure, probably as a consequence of the lack of structural data at the atomic level of detail. Herein, as a result of five independent molecular dynamics simulations, three different binding sites were found for xenon in the glycine binding domain of the Nmethyl-D-aspartate receptor. The absolute binding free energy of xenon in these sites ranges between -8 and -14 kJ·mole−1. However, it depends significantly upon the protein conformer chosen for performing the calculation, suggesting that larger values could probably be obtained, if other conformers were considered. These three sites are next to each other, one of them being next to the glycine site. This could explain why the F758W and F758Y mutations can prevent competitive inhibition by xenon without affecting glycine binding.},
note = {arXiv: 2203.02219},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Xenon can produce general anesthesia. Its main protein target is the N-methyl-D-aspartate receptor, a ionotropic channel playing a pivotal role in the function of the central nervous system. The molecular mechanisms allowing this noble gas to have such a specific effect remain obscure, probably as a consequence of the lack of structural data at the atomic level of detail. Herein, as a result of five independent molecular dynamics simulations, three different binding sites were found for xenon in the glycine binding domain of the Nmethyl-D-aspartate receptor. The absolute binding free energy of xenon in these sites ranges between -8 and -14 kJ·mole−1. However, it depends significantly upon the protein conformer chosen for performing the calculation, suggesting that larger values could probably be obtained, if other conformers were considered. These three sites are next to each other, one of them being next to the glycine site. This could explain why the F758W and F758Y mutations can prevent competitive inhibition by xenon without affecting glycine binding.
3 publications
Teze, David; Zhao, Jiao; Wiemann, Mathias; Ara, Kazi Z G; Lupo, Rossana; Zeuner, Birgitte; Vuillemin, Marlène; Rønne, Mette E; Carlström, Göran; Duus, Jens Ø; Sanejouand, Yves-Henri; O'Donohue, Michael J; Karlsson, Eva Nordberg; Fauré, Régis; Stålbrand, Henrik; Svensson, Birte
Rational Enzyme Design without Structural Knowledge: A Sequence-Based Approach for Efficient Generation of Transglycosylases Article de journal
Dans: Chemistry – A European Journal, vol. 27, no. 40, p. 10323–10334, 2021, ISSN: 0947-6539, 1521-3765.
@article{https://doi.org/10.1002/chem.202100110,
title = {Rational Enzyme Design without Structural Knowledge: A Sequence-Based Approach for Efficient Generation of Transglycosylases},
author = {David Teze and Jiao Zhao and Mathias Wiemann and Kazi Z G Ara and Rossana Lupo and Birgitte Zeuner and Marlène Vuillemin and Mette E Rønne and Göran Carlström and Jens Ø Duus and Yves-Henri Sanejouand and Michael J O'Donohue and Eva Nordberg Karlsson and Régis Fauré and Henrik Stålbrand and Birte Svensson},
url = {https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202100110},
doi = {https://doi.org/10.1002/chem.202100110},
issn = {0947-6539, 1521-3765},
year = {2021},
date = {2021-04-29},
urldate = {2021-04-29},
journal = {Chemistry – A European Journal},
volume = {27},
number = {40},
pages = {10323--10334},
abstract = {Glycobiology is dogged by the relative scarcity of synthetic, defined oligosaccharides. Enzyme-catalysed glycosylation using glycoside hydrolases is feasible but is hampered by the innate hydrolytic activity of these enzymes. Protein engineering is useful to remedy this, but it usually requires prior structural knowledge of the target enzyme, and/or relies on extensive, time-consuming screening and analysis. Here we describe a straightforward strategy that involves rational rapid in silico analysis of protein sequences. The method pinpoints 6‒12 single mutant candidates to improve transglycosylation yields. Requiring very little prior knowledge of the target enzyme other than its sequence, the method is generic and procures catalysts for the formation of glycosidic bonds involving various d / l -, α/β-pyranosides or furanosides, and exo - and endo -action. Moreover, mutations validated in one enzyme can be transposed to others, even distantly related enzymes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Glycobiology is dogged by the relative scarcity of synthetic, defined oligosaccharides. Enzyme-catalysed glycosylation using glycoside hydrolases is feasible but is hampered by the innate hydrolytic activity of these enzymes. Protein engineering is useful to remedy this, but it usually requires prior structural knowledge of the target enzyme, and/or relies on extensive, time-consuming screening and analysis. Here we describe a straightforward strategy that involves rational rapid in silico analysis of protein sequences. The method pinpoints 6‒12 single mutant candidates to improve transglycosylation yields. Requiring very little prior knowledge of the target enzyme other than its sequence, the method is generic and procures catalysts for the formation of glycosidic bonds involving various d / l -, α/β-pyranosides or furanosides, and exo - and endo -action. Moreover, mutations validated in one enzyme can be transposed to others, even distantly related enzymes.
Sanejouand, Yves-Henri
Normal-mode driven exploration of protein domain motions Article de journal
Dans: J. Comput. Chem., vol. 42, p. 2250, 2021.
@article{sanejouand2021normalmode,
title = {Normal-mode driven exploration of protein domain motions},
author = {Yves-Henri Sanejouand},
url = {https://arxiv.org/abs/2103.11959},
doi = {10.1002/jcc.26755},
year = {2021},
date = {2021-03-22},
urldate = {2021-03-22},
journal = {J. Comput. Chem.},
volume = {42},
pages = {2250},
abstract = {Domain motions involved in the function of proteins can often be well described as a combination of motions along a handfull of low-frequency modes, that is, with the values of a few normal coordinates. This means that, when the functional motion of a protein is unknown, it should prove possible to predict it, since it amounts to guess a few values. However, without the help of additional experimental data, using normal coordinates for generating accurate conformers far away from the initial one is not so straightforward. To do so, a new approach is proposed: instead of building conformers directly with the values of a subset of normal coordinates, they are built in two steps, the conformer built with normal coordinates being just used for defining a set of distance constraints, the final conformer being built so as to match them. Note that this approach amounts to transform the problem of generating accurate protein conformers using normal coordinates into a better known one: the distance-geometry problem, which is herein solved with the help of the ROSETTA software. In the present study, this approach allowed to rebuild accurately six large amplitude conformational changes, using at most six low-frequency normal coordinates. As a consequence of the low-dimensionality of the corresponding subspace, random exploration also proved enough for generating low-energy conformers close to the known end-point of the conformational change of the LAO binding protein, lysozyme T4 and adenylate kinase.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Domain motions involved in the function of proteins can often be well described as a combination of motions along a handfull of low-frequency modes, that is, with the values of a few normal coordinates. This means that, when the functional motion of a protein is unknown, it should prove possible to predict it, since it amounts to guess a few values. However, without the help of additional experimental data, using normal coordinates for generating accurate conformers far away from the initial one is not so straightforward. To do so, a new approach is proposed: instead of building conformers directly with the values of a subset of normal coordinates, they are built in two steps, the conformer built with normal coordinates being just used for defining a set of distance constraints, the final conformer being built so as to match them. Note that this approach amounts to transform the problem of generating accurate protein conformers using normal coordinates into a better known one: the distance-geometry problem, which is herein solved with the help of the ROSETTA software. In the present study, this approach allowed to rebuild accurately six large amplitude conformational changes, using at most six low-frequency normal coordinates. As a consequence of the low-dimensionality of the corresponding subspace, random exploration also proved enough for generating low-energy conformers close to the known end-point of the conformational change of the LAO binding protein, lysozyme T4 and adenylate kinase.
Sanejouand, Yves-Henri
On the vibrational free energy of hydrated proteins Article de journal
Dans: Physical Biology, vol. 18, no. 3, p. 036003, 2021.
@article{Sanejouand_2021,
title = {On the vibrational free energy of hydrated proteins},
author = {Yves-Henri Sanejouand},
url = {https://doi.org/10.1088/1478-3975/abdc0f},
doi = {10.1088/1478-3975/abdc0f},
year = {2021},
date = {2021-03-01},
urldate = {2021-03-01},
journal = {Physical Biology},
volume = {18},
number = {3},
pages = {036003},
publisher = {IOP Publishing},
abstract = {When the hydration shell of a protein is filled with at least 0.6 gram of water per gram of protein, a significant anti-correlation between the vibrational free energy and the potential energy of energy-minimized conformers is observed. This means that low potential energy, well-hydrated, protein conformers tend to be more rigid than high-energy ones. On the other hand, in the case of CASP target 624, when its hydration shell is filled, a significant energy gap is observed between the crystal structure and the best conformers proposed during the prediction experiment, strongly suggesting that including explicit water molecules may help identifying unlikely conformers among good-looking ones.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
When the hydration shell of a protein is filled with at least 0.6 gram of water per gram of protein, a significant anti-correlation between the vibrational free energy and the potential energy of energy-minimized conformers is observed. This means that low potential energy, well-hydrated, protein conformers tend to be more rigid than high-energy ones. On the other hand, in the case of CASP target 624, when its hydration shell is filled, a significant energy gap is observed between the crystal structure and the best conformers proposed during the prediction experiment, strongly suggesting that including explicit water molecules may help identifying unlikely conformers among good-looking ones.
2 publications
Dhingra, Surbhi; Sowdhamini, Ramanathan; Sanejouand, Yves-Henri; Cadet, Frédéric; Offmann, Bernard
Customised fragment libraries for ab initio protein structure prediction using a structural alphabet Article de journal
Dans: arXiv:2005.01696, 2020.
@article{Dhingra2020,
title = {Customised fragment libraries for ab initio protein structure prediction using a structural alphabet},
author = {Surbhi Dhingra and Ramanathan Sowdhamini and Yves-Henri Sanejouand and Frédéric Cadet and Bernard Offmann},
url = {https://arxiv.org/pdf/2005.01696.pdf},
year = {2020},
date = {2020-05-01},
journal = {arXiv:2005.01696},
abstract = {Motivation: Computational protein structure prediction has taken over the structural community in past few decades, mostly focusing on the development of Template-Free modelling (TFM) or ab initio modelling protocols. Fragment-based assembly (FBA), falls under this category and is by far the most popular approach to solve the spatial arrangements of proteins. FBA approaches usually rely on sequence based profile comparison to generate fragments from a representative structural database. Here we report the use of Protein Blocks (PBs), a structural alphabet (SA) to perform such sequence comparison and to build customised fragment libraries for TFM. Results: We demonstrate that predicted PB sequences for a query protein can be used to search for high quality fragments that overall cover above 90% of the query. The fragments generated are of minimum length of 11 residues, and fragments that cover more than 30% of the query length were often obtained. Our work shows that PBs can serve as a good way to extract structurally similar fragments from a database of representatives of non-homologous structures and of the proteins that contain less ordered regions.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Motivation: Computational protein structure prediction has taken over the structural community in past few decades, mostly focusing on the development of Template-Free modelling (TFM) or ab initio modelling protocols. Fragment-based assembly (FBA), falls under this category and is by far the most popular approach to solve the spatial arrangements of proteins. FBA approaches usually rely on sequence based profile comparison to generate fragments from a representative structural database. Here we report the use of Protein Blocks (PBs), a structural alphabet (SA) to perform such sequence comparison and to build customised fragment libraries for TFM. Results: We demonstrate that predicted PB sequences for a query protein can be used to search for high quality fragments that overall cover above 90% of the query. The fragments generated are of minimum length of 11 residues, and fragments that cover more than 30% of the query length were often obtained. Our work shows that PBs can serve as a good way to extract structurally similar fragments from a database of representatives of non-homologous structures and of the proteins that contain less ordered regions.
Hendrickx, Johann; Tran, Vinh; Sanejouand, Yves-Henri
Numerous severely twisted N-acetylglucosamine conformations found in the protein databank Article de journal
Dans: Proteins: Structure, Function and Bioinformatics, vol. 88, no. 10, p. 1376–1383, 2020, ISSN: 10970134.
@article{Hendrickx2020,
title = {Numerous severely twisted N-acetylglucosamine conformations found in the protein databank},
author = {Johann Hendrickx and Vinh Tran and Yves-Henri Sanejouand},
doi = {10.1002/prot.25957},
issn = {10970134},
year = {2020},
date = {2020-01-01},
journal = {Proteins: Structure, Function and Bioinformatics},
volume = {88},
number = {10},
pages = {1376--1383},
abstract = {Taking advantage of the known planarity of the N-acetyl group of N-acetylglucosamine, an analysis of the quality of carbohydrate structures found in the protein databank was performed. Few obvious defects of the local geometry of the carbonyl group were observed. However, the N-acetyl group was often found in the less favorable cis conformation (12% of the cases). It was also found severely twisted in numerous instances, especially in structures with a resolution poorer than 1.9 Å determined between 2000 and 2015. Though the automated PDB-REDO procedure has proved able to improve nearly 85% of the structural models deposited to the PDB, and does prove able to cure most severely twisted conformations of the N-acetyl group, it fails to correct its high rate of cis conformations. More generally, for structures with a resolution poorer than 1.6 Å, it produces N-acetylglucosamine models in slightly poorer agreement with experimental data, as measured using real-space correlation coefficients. Significant improvements are thus still needed, at least as far as this carbohydrate structure is concerned.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Taking advantage of the known planarity of the N-acetyl group of N-acetylglucosamine, an analysis of the quality of carbohydrate structures found in the protein databank was performed. Few obvious defects of the local geometry of the carbonyl group were observed. However, the N-acetyl group was often found in the less favorable cis conformation (12% of the cases). It was also found severely twisted in numerous instances, especially in structures with a resolution poorer than 1.9 Å determined between 2000 and 2015. Though the automated PDB-REDO procedure has proved able to improve nearly 85% of the structural models deposited to the PDB, and does prove able to cure most severely twisted conformations of the N-acetyl group, it fails to correct its high rate of cis conformations. More generally, for structures with a resolution poorer than 1.6 Å, it produces N-acetylglucosamine models in slightly poorer agreement with experimental data, as measured using real-space correlation coefficients. Significant improvements are thus still needed, at least as far as this carbohydrate structure is concerned.
1 publication
David, Benoit; Arnaud, Philippe; Tellier, Charles; Sanejouand, Yves-Henri
Toward the design of efficient transglycosidases: the case of the GH1 of Thermus thermophilus Article de journal
Dans: Protein Engineering, Design and Selection, vol. 32, no. 7, p. 309–316, 2019, ISSN: 1741-0126.
@article{10.1093/protein/gzz032,
title = {Toward the design of efficient transglycosidases: the case of the GH1 of Thermus thermophilus},
author = {Benoit David and Philippe Arnaud and Charles Tellier and Yves-Henri Sanejouand},
url = {https://doi.org/10.1093/protein/gzz032},
doi = {10.1093/protein/gzz032},
issn = {1741-0126},
year = {2019},
date = {2019-01-01},
journal = {Protein Engineering, Design and Selection},
volume = {32},
number = {7},
pages = {309--316},
abstract = {Using the information available in the sequences of well-characterized transglycosidases found in plants, mutations were introduced in the glycoside hydrolase of the bacterium Thermus thermophilus, with the aim of turning it into an efficient transglycosidase. All mutants happen to have fair catalytic efficiencies, being at worst 25 times less efficient than the wild type. Noteworthy, W120F, one of our high transglycosylation yield (≈ 50%) mutants, is only two times less efficient than the wild type. Interestingly, while in the wild type the sidechain of the acid–base is only found able to sample a pair of equivalent conformations during 0.5-µs-long molecular dynamics simulations, its flexibility is much higher in the case of the high transglycosylation yield mutants. Our results thus suggest that engineering the flexibility of the acid–base of a retaining glycoside hydrolase could be a general way to turn it into an efficient transglycosidase.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Using the information available in the sequences of well-characterized transglycosidases found in plants, mutations were introduced in the glycoside hydrolase of the bacterium Thermus thermophilus, with the aim of turning it into an efficient transglycosidase. All mutants happen to have fair catalytic efficiencies, being at worst 25 times less efficient than the wild type. Noteworthy, W120F, one of our high transglycosylation yield (≈ 50%) mutants, is only two times less efficient than the wild type. Interestingly, while in the wild type the sidechain of the acid–base is only found able to sample a pair of equivalent conformations during 0.5-µs-long molecular dynamics simulations, its flexibility is much higher in the case of the high transglycosylation yield mutants. Our results thus suggest that engineering the flexibility of the acid–base of a retaining glycoside hydrolase could be a general way to turn it into an efficient transglycosidase.
5 publications
Vetrivel, Iyanar; Mahajan, Swapnil; Tyagi, Manoj; Hoffmann, Lionel; Sanejouand, Yves-Henri; Srinivasan, Narayanaswamy; Brevern, Alexandre G De; Cadet, Frédéric; Offmann, Bernard
Knowledge-based prediction of protein backbone conformation using a structural alphabet Article de journal
Dans: PLoS ONE, vol. 12, no. 11, 2017, ISSN: 19326203.
@article{Vetrivel2017,
title = {Knowledge-based prediction of protein backbone conformation using a structural alphabet},
author = {Iyanar Vetrivel and Swapnil Mahajan and Manoj Tyagi and Lionel Hoffmann and Yves-Henri Sanejouand and Narayanaswamy Srinivasan and Alexandre G {De Brevern} and Frédéric Cadet and Bernard Offmann},
doi = {10.1371/journal.pone.0186215},
issn = {19326203},
year = {2017},
date = {2017-11-01},
journal = {PLoS ONE},
volume = {12},
number = {11},
publisher = {Public Library of Science},
abstract = {Libraries of structural prototypes that abstract protein local structures are known as structural alphabets and have proven to be very useful in various aspects of protein structure analyses and predictions. One such library, Protein Blocks, is composed of 16 standard 5-residues long structural prototypes. This form of analyzing proteins involves drafting its structure as a string of Protein Blocks. Predicting the local structure of a protein in terms of protein blocks is the general objective of this work. A new approach, PB-kPRED is proposed towards this aim. It involves (i) organizing the structural knowledge in the form of a database of pentapeptide fragments extracted from all protein structures in the PDB and (ii) applying a knowledge-based algorithm that does not rely on any secondary structure predictions and/ or sequence alignment profiles, to scan this database and predict most probable backbone conformations for the protein local structures. Though PB-kPRED uses the structural information from homologues in preference, if available. The predictions were evaluated rigorously on 15,544 query proteins representing a non-redundant subset of the PDB filtered at 30% sequence identity cut-off. We have shown that the kPRED method was able to achieve mean accuracies ranging from 40.8% to 66.3% depending on the availability of homologues. The impact of the different strategies for scanning the database on the prediction was evaluated and is discussed. Our results highlight the usefulness of the method in the context of proteins without any known structural homologues. A scoring function that gives a good estimate of the accuracy of prediction was further developed. This score estimates very well the accuracy of the algorithm (R2 of 0.82). An online version of the tool is provided freely for non-commercial usage at http://www.bo-protscience.fr/kpred/.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Libraries of structural prototypes that abstract protein local structures are known as structural alphabets and have proven to be very useful in various aspects of protein structure analyses and predictions. One such library, Protein Blocks, is composed of 16 standard 5-residues long structural prototypes. This form of analyzing proteins involves drafting its structure as a string of Protein Blocks. Predicting the local structure of a protein in terms of protein blocks is the general objective of this work. A new approach, PB-kPRED is proposed towards this aim. It involves (i) organizing the structural knowledge in the form of a database of pentapeptide fragments extracted from all protein structures in the PDB and (ii) applying a knowledge-based algorithm that does not rely on any secondary structure predictions and/ or sequence alignment profiles, to scan this database and predict most probable backbone conformations for the protein local structures. Though PB-kPRED uses the structural information from homologues in preference, if available. The predictions were evaluated rigorously on 15,544 query proteins representing a non-redundant subset of the PDB filtered at 30% sequence identity cut-off. We have shown that the kPRED method was able to achieve mean accuracies ranging from 40.8% to 66.3% depending on the availability of homologues. The impact of the different strategies for scanning the database on the prediction was evaluated and is discussed. Our results highlight the usefulness of the method in the context of proteins without any known structural homologues. A scoring function that gives a good estimate of the accuracy of prediction was further developed. This score estimates very well the accuracy of the algorithm (R2 of 0.82). An online version of the tool is provided freely for non-commercial usage at http://www.bo-protscience.fr/kpred/.
Sanejouand, Yves-Henri
Mutational dynamics of influenza A viruses: a principal component analysis of hemagglutinin sequences of subtype H1 Article de journal
Dans: 2017.
@article{Sanejouand2017b,
title = {Mutational dynamics of influenza A viruses: a principal component analysis of hemagglutinin sequences of subtype H1},
author = {Yves-Henri Sanejouand},
url = {http://arxiv.org/abs/1710.01594},
year = {2017},
date = {2017-10-01},
abstract = {A principal component analysis of a multiple sequence alignement of hemagglutinin sequences of subtype H1 has been performed, the sequences being encoded using the amino-acid property that maximizes the weight of the major component. In the case of this alignment, it happens to be a well-known hydrophobicity scale. Interestingly, sequences coming from human have large positive amplitudes along the major component before 2009, and large negative ones afterwards. This means that the 2009 pandemic was associated to a major change in the hydrophobicity pattern of hemagglutinin. The present analysis also highlights the high variability of viral sequences coming from swine. At a more general level, the method proposed in this paper allows to describe a sequence coming from an alignment with a set of numbers, the original point being that the choice of the corresponding property is driven by the data. This approach should allow the application of numerous methods to the study of large multiple sequence alignments.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
A principal component analysis of a multiple sequence alignement of hemagglutinin sequences of subtype H1 has been performed, the sequences being encoded using the amino-acid property that maximizes the weight of the major component. In the case of this alignment, it happens to be a well-known hydrophobicity scale. Interestingly, sequences coming from human have large positive amplitudes along the major component before 2009, and large negative ones afterwards. This means that the 2009 pandemic was associated to a major change in the hydrophobicity pattern of hemagglutinin. The present analysis also highlights the high variability of viral sequences coming from swine. At a more general level, the method proposed in this paper allows to describe a sequence coming from an alignment with a set of numbers, the original point being that the choice of the corresponding property is driven by the data. This approach should allow the application of numerous methods to the study of large multiple sequence alignments.
Sanejouand, Yves-Henri
A singular mutation in the hemagglutinin of the 1918 pandemic virus Article de journal
Dans: Archives of Biochemistry and Biophysics, vol. 625-626, p. 13–16, 2017, ISSN: 0003-9861.
@article{SANEJOUAND201713,
title = {A singular mutation in the hemagglutinin of the 1918 pandemic virus},
author = {Yves-Henri Sanejouand},
url = {http://www.sciencedirect.com/science/article/pii/S0003986117302576},
doi = {https://doi.org/10.1016/j.abb.2017.05.013},
issn = {0003-9861},
year = {2017},
date = {2017-01-01},
journal = {Archives of Biochemistry and Biophysics},
volume = {625-626},
pages = {13--16},
abstract = {The influenza pandemic of 1918–1919 killed at least 50 million people. The reasons why this pandemic was so deadly remain largely unknown [9]. However, It has been shown that the 1918 viral hemagglutinin allows to reproduce the hallmarks of the illness observed during the original pandemic [11]. Thanks to the wealth of hemagglutinin sequences accumulated over the last decades, amino-acid substitutions that are found in the 1918–1919 sequences but rare otherwise can be identified with high confidence. Noteworthy, Gly 188, which is located within a key motif of the receptor binding site, has never been observed again in sequences of human viruses of subtype H1. Monitoring this singular mutation in viral sequences may help prevent another dramatic pandemic.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The influenza pandemic of 1918–1919 killed at least 50 million people. The reasons why this pandemic was so deadly remain largely unknown [9]. However, It has been shown that the 1918 viral hemagglutinin allows to reproduce the hallmarks of the illness observed during the original pandemic [11]. Thanks to the wealth of hemagglutinin sequences accumulated over the last decades, amino-acid substitutions that are found in the 1918–1919 sequences but rare otherwise can be identified with high confidence. Noteworthy, Gly 188, which is located within a key motif of the receptor binding site, has never been observed again in sequences of human viruses of subtype H1. Monitoring this singular mutation in viral sequences may help prevent another dramatic pandemic.
Mahajan, Swapnil; Sanejouand, Yves-Henri
Jumping between protein conformers using normal modes Article de journal
Dans: Journal of Computational Chemistry, vol. 38, no. 18, p. 1622–1630, 2017, ISSN: 1096987X.
@article{Mahajan2017,
title = {Jumping between protein conformers using normal modes},
author = {Swapnil Mahajan and Yves-Henri Sanejouand},
doi = {10.1002/jcc.24803},
issn = {1096987X},
year = {2017},
date = {2017-01-01},
journal = {Journal of Computational Chemistry},
volume = {38},
number = {18},
pages = {1622--1630},
abstract = {The relationship between the normal modes of a protein and its functional conformational change has been studied for decades. However, using this relationship in a predictive context remains a challenge. In this work, we demonstrate that, starting from a given protein conformer, it is possible to generate in a single step model conformers that are less than 1 Å (Cα-RMSD) from the conformer which is the known endpoint of the conformational change, particularly when the conformational change is collective in nature. Such accurate model conformers can be generated by following either the so-called robust or the 50 lowest-frequency modes obtained with various Elastic Network Models (ENMs). Interestingly, the quality of many of these models compares well with actual crystal structures, as assessed by the ROSETTA scoring function and PROCHECK. The most accurate and best quality conformers obtained in the present study were generated by using the 50 lowest-frequency modes of an all-atom ENM. However, with less than ten robust modes, which are identified without any prior knowledge of the nature of the conformational change, nearly 90% of the motion described by the 50 lowest-frequency modes of a protein can be captured. Such results strongly suggest that exploring the robust modes of ENMs may prove efficient for sampling the functionally relevant conformational repertoire of many proteins. textcopyright 2017 Wiley Periodicals, Inc.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The relationship between the normal modes of a protein and its functional conformational change has been studied for decades. However, using this relationship in a predictive context remains a challenge. In this work, we demonstrate that, starting from a given protein conformer, it is possible to generate in a single step model conformers that are less than 1 Å (Cα-RMSD) from the conformer which is the known endpoint of the conformational change, particularly when the conformational change is collective in nature. Such accurate model conformers can be generated by following either the so-called robust or the 50 lowest-frequency modes obtained with various Elastic Network Models (ENMs). Interestingly, the quality of many of these models compares well with actual crystal structures, as assessed by the ROSETTA scoring function and PROCHECK. The most accurate and best quality conformers obtained in the present study were generated by using the 50 lowest-frequency modes of an all-atom ENM. However, with less than ten robust modes, which are identified without any prior knowledge of the nature of the conformational change, nearly 90% of the motion described by the 50 lowest-frequency modes of a protein can be captured. Such results strongly suggest that exploring the robust modes of ENMs may prove efficient for sampling the functionally relevant conformational repertoire of many proteins. textcopyright 2017 Wiley Periodicals, Inc.
David, Benoit; Irague, Romain; Jouanneau, Diane; Daligault, Franck; Czjzek, Mirjam; Sanejouand, Yves-Henri; Tellier, Charles
Internal Water Dynamics Control the Transglycosylation/Hydrolysis Balance in the Agarase (AgaD) of Zobellia galactanivorans Article de journal
Dans: ACS Catalysis, vol. 7, no. 5, p. 3357–3367, 2017, ISSN: 21555435.
@article{David2017a,
title = {Internal Water Dynamics Control the Transglycosylation/Hydrolysis Balance in the Agarase (AgaD) of Zobellia galactanivorans},
author = {Benoit David and Romain Irague and Diane Jouanneau and Franck Daligault and Mirjam Czjzek and Yves-Henri Sanejouand and Charles Tellier},
doi = {10.1021/acscatal.7b00348},
issn = {21555435},
year = {2017},
date = {2017-01-01},
journal = {ACS Catalysis},
volume = {7},
number = {5},
pages = {3357--3367},
abstract = {In retaining glycoside hydrolases (GHs), transglycosylase activity is often low due to the natural hydrolytic activity that is favored in water. Improving the relative transglycosylase activity of these enzymes is of particular interest to obtain enzymes suitable for the synthesis of oligosaccharides. We explored the effect of engineering the water dynamics within the endo-β-agarase AgaD on the transglycosylation/hydrolysis (T/H) balance. By mutating three amino acids (D341, Q342, and S351), which could control water access to a putative water channel ending close to the active site, we obtained AgaD variants with an inverted T/H balance. For the best mutant, D341L/Q342H/S351F, the hydrolysis activity was reduced 50-fold in comparison to the wild type, while the transglycosylase activity was maintained and even slightly improved. This variant produced a large amount of oligo-agaroses by a disproportionation reaction with deca-agarose as the substrate. Molecular dynamics simulations showed that these enzymatic modifications were correlated with higher water dynamics, as revealed by a marked reduction in the water survival time and a decrease in the purge time of water in a channel ending close to the active site. These results suggest that modifying the water dynamics in GHs could be a rational basis for engineering of transglycosylase activity.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In retaining glycoside hydrolases (GHs), transglycosylase activity is often low due to the natural hydrolytic activity that is favored in water. Improving the relative transglycosylase activity of these enzymes is of particular interest to obtain enzymes suitable for the synthesis of oligosaccharides. We explored the effect of engineering the water dynamics within the endo-β-agarase AgaD on the transglycosylation/hydrolysis (T/H) balance. By mutating three amino acids (D341, Q342, and S351), which could control water access to a putative water channel ending close to the active site, we obtained AgaD variants with an inverted T/H balance. For the best mutant, D341L/Q342H/S351F, the hydrolysis activity was reduced 50-fold in comparison to the wild type, while the transglycosylase activity was maintained and even slightly improved. This variant produced a large amount of oligo-agaroses by a disproportionation reaction with deca-agarose as the substrate. Molecular dynamics simulations showed that these enzymatic modifications were correlated with higher water dynamics, as revealed by a marked reduction in the water survival time and a decrease in the purge time of water in a channel ending close to the active site. These results suggest that modifying the water dynamics in GHs could be a rational basis for engineering of transglycosylase activity.
4 publications
Mahajan, Swapnil; Brevern, Alexandre G De; Sanejouand, Yves-Henri; Srinivasan, Narayanaswamy; Offmann, Bernard
Use of a structural alphabet to find compatible folds for amino acid sequences Article de journal
Dans: Protein Science, vol. 24, no. 1, p. 145–153, 2015, ISSN: 1469896X.
@article{Mahajan2015a,
title = {Use of a structural alphabet to find compatible folds for amino acid sequences},
author = {Swapnil Mahajan and Alexandre G {De Brevern} and Yves-Henri Sanejouand and Narayanaswamy Srinivasan and Bernard Offmann},
doi = {10.1002/pro.2581},
issn = {1469896X},
year = {2015},
date = {2015-01-01},
journal = {Protein Science},
volume = {24},
number = {1},
pages = {145--153},
abstract = {The structural annotation of proteins with no detectable homologs of known 3D structure identified using sequence-search methods is a major challenge today. We propose an original method that computes the conditional probabilities for the amino-acid sequence of a protein to fit to known protein 3D structures using a structural alphabet, known as "Protein Blocks" (PBs). PBs constitute a library of 16 local structural prototypes that approximate every part of protein backbone structures. It is used to encode 3D protein structures into 1D PB sequences and to capture sequence to structure relationships. Our method relies on amino acid occurrence matrices, one for each PB, to score global and local threading of query amino acid sequences to protein folds encoded into PB sequences. It does not use any information from residue contacts or sequence-search methods or explicit incorporation of hydrophobic effect. The performance of the method was assessed with independent test datasets derived from SCOP 1.75A. With a Z-score cutoff that achieved 95% specificity (i.e., less than 5% false positives), global and local threading showed sensitivity of 64.1% and 34.2%, respectively. We further tested its performance on 57 difficult CASP10 targets that had no known homologs in PDB: 38 compatible templates were identified by our approach and 66% of these hits yielded correctly predicted structures. This method scales-up well and offers promising perspectives for structural annotations at genomic level. It has been implemented in the form of a web-server that is freely available at http://www.bo-protscience.fr/forsa.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The structural annotation of proteins with no detectable homologs of known 3D structure identified using sequence-search methods is a major challenge today. We propose an original method that computes the conditional probabilities for the amino-acid sequence of a protein to fit to known protein 3D structures using a structural alphabet, known as "Protein Blocks" (PBs). PBs constitute a library of 16 local structural prototypes that approximate every part of protein backbone structures. It is used to encode 3D protein structures into 1D PB sequences and to capture sequence to structure relationships. Our method relies on amino acid occurrence matrices, one for each PB, to score global and local threading of query amino acid sequences to protein folds encoded into PB sequences. It does not use any information from residue contacts or sequence-search methods or explicit incorporation of hydrophobic effect. The performance of the method was assessed with independent test datasets derived from SCOP 1.75A. With a Z-score cutoff that achieved 95% specificity (i.e., less than 5% false positives), global and local threading showed sensitivity of 64.1% and 34.2%, respectively. We further tested its performance on 57 difficult CASP10 targets that had no known homologs in PDB: 38 compatible templates were identified by our approach and 66% of these hits yielded correctly predicted structures. This method scales-up well and offers promising perspectives for structural annotations at genomic level. It has been implemented in the form of a web-server that is freely available at http://www.bo-protscience.fr/forsa.
Mahajan, Swapnil; Sanejouand, Yves-Henri
On the relationship between low-frequency normal modes and the large-scale conformational changes of proteins Article de journal
Dans: Archives of Biochemistry and Biophysics, vol. 567, p. 59–65, 2015, ISSN: 10960384.
@article{Mahajan2015b,
title = {On the relationship between low-frequency normal modes and the large-scale conformational changes of proteins},
author = {Swapnil Mahajan and Yves-Henri Sanejouand},
url = {http://dx.doi.org/10.1016/j.abb.2014.12.020},
doi = {10.1016/j.abb.2014.12.020},
issn = {10960384},
year = {2015},
date = {2015-01-01},
journal = {Archives of Biochemistry and Biophysics},
volume = {567},
pages = {59--65},
publisher = {Elsevier Inc.},
abstract = {Normal mode analysis is a computational technique that allows to study the dynamics of biological macromolecules. It was first applied to small protein cases, more than thirty years ago. The interest in this technique then raised when it was realized that it can provide insights about the large-scale conformational changes a protein can experience, for instance upon ligand binding. As it was also realized that studying highly simplified protein models can provide similar insights, meaning that this kind of analysis can be both quick and simple to handle, several applications were proposed, in the context of various structural biology techniques. This review focuses on these applications, as well as on how the functional relevance of the lowest-frequency modes of proteins was established.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Normal mode analysis is a computational technique that allows to study the dynamics of biological macromolecules. It was first applied to small protein cases, more than thirty years ago. The interest in this technique then raised when it was realized that it can provide insights about the large-scale conformational changes a protein can experience, for instance upon ligand binding. As it was also realized that studying highly simplified protein models can provide similar insights, meaning that this kind of analysis can be both quick and simple to handle, several applications were proposed, in the context of various structural biology techniques. This review focuses on these applications, as well as on how the functional relevance of the lowest-frequency modes of proteins was established.
Sanejouand, Yves-Henri
Simplified flexibility analysis of proteins Chapitre d'ouvrage
Dans: Fuxreiter, Monika (Ed.): Computational Approaches to Protein Dynamics: From Quantum to Coarse-Grained Methods, Chapitre 5, p. 153–182, CRC Press, 2015.
@inbook{EQ1:SANEJOUAND:2015,
title = {Simplified flexibility analysis of proteins},
author = {Yves-Henri Sanejouand},
editor = {Monika Fuxreiter},
url = {http://arxiv.org/abs/1312.5639},
year = {2015},
date = {2015-01-01},
booktitle = {Computational Approaches to Protein Dynamics: From Quantum to Coarse-Grained Methods},
pages = {153--182},
publisher = {CRC Press},
chapter = {5},
abstract = {A simple way to get insights about the possible functional motions of a protein is to perform a normal mode analysis (NMA). Indeed, it has been shown that low-frequency modes thus obtained are often closely related to domain motions involved in protein function. Moreover, because protein low-frequency modes are known to be robust, NMA can be performed using coarse-grained models. As a consequence, it can be done for large ensembles of conformations as well as for large systems, like the ribosome, whole virus capsids, etc. Unexpectedly, on the high-frequency side, modes obtained with cutoff-based coarse-grained models also seem able to provide useful insights on protein dynamical properties.},
keywords = {},
pubstate = {published},
tppubtype = {inbook}
}
A simple way to get insights about the possible functional motions of a protein is to perform a normal mode analysis (NMA). Indeed, it has been shown that low-frequency modes thus obtained are often closely related to domain motions involved in protein function. Moreover, because protein low-frequency modes are known to be robust, NMA can be performed using coarse-grained models. As a consequence, it can be done for large ensembles of conformations as well as for large systems, like the ribosome, whole virus capsids, etc. Unexpectedly, on the high-frequency side, modes obtained with cutoff-based coarse-grained models also seem able to provide useful insights on protein dynamical properties.
Teze, David; Daligault, Franck; Ferrières, Vincent; Sanejouand, Yves-Henri; Tellier, Charles
Semi-rational approach for converting a GH36 α-glycosidase into an α-transglycosidase Article de journal
Dans: Glycobiology, vol. 25, no. 4, p. 420–427, 2015, ISSN: 14602423.
@article{Teze2015,
title = {Semi-rational approach for converting a GH36 α-glycosidase into an α-transglycosidase},
author = {David Teze and Franck Daligault and Vincent Ferrières and Yves-Henri Sanejouand and Charles Tellier},
doi = {10.1093/glycob/cwu124},
issn = {14602423},
year = {2015},
date = {2015-01-01},
journal = {Glycobiology},
volume = {25},
number = {4},
pages = {420--427},
abstract = {A large number of retaining glycosidases catalyze both hydrolysis and transglycosylation reactions. In order to use them as catalysts for oligosaccharide synthesis, the balance between these two competing reactions has to be shifted toward transglycosylation. We previously designed a semi-rational approach to convert the Thermus thermophilus β-glycosidases into transglycosidases by mutating highly conserved residues located around the -1 subsite. In an attempt to verify that this strategy could be a generic approach to turn glycosidases into transglycosidases, Geobacillus stearothermophilus α-galactosidase (AgaB) was selected in order to obtain α-transgalactosidases. This is of particular interest as, to date, there are no efficient α-galactosynthases, despite the considerable importance of α-galactooligosaccharides. Thus, by site-directed mutagenesis on 14 AgaB residues, 26 single mutants and 22 double mutants were created and screened, of which 11 single mutants and 6 double mutants exhibited improved synthetic activity, producing 4-nitrophenyl α-d-galactopyranosyl-(1,6)-α-d-galactopyranoside in 26-57% yields against only 22% when native AgaB was used. It is interesting to note that the best variant was obtained by mutating a second-shell residue, with no direct interaction with the substrate or a catalytic amino acid. As this approach has proved to be efficient with both α- and β-glycosidases, it is a promising route to convert retaining glycosidases into transglycosidases.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
A large number of retaining glycosidases catalyze both hydrolysis and transglycosylation reactions. In order to use them as catalysts for oligosaccharide synthesis, the balance between these two competing reactions has to be shifted toward transglycosylation. We previously designed a semi-rational approach to convert the Thermus thermophilus β-glycosidases into transglycosidases by mutating highly conserved residues located around the -1 subsite. In an attempt to verify that this strategy could be a generic approach to turn glycosidases into transglycosidases, Geobacillus stearothermophilus α-galactosidase (AgaB) was selected in order to obtain α-transgalactosidases. This is of particular interest as, to date, there are no efficient α-galactosynthases, despite the considerable importance of α-galactooligosaccharides. Thus, by site-directed mutagenesis on 14 AgaB residues, 26 single mutants and 22 double mutants were created and screened, of which 11 single mutants and 6 double mutants exhibited improved synthetic activity, producing 4-nitrophenyl α-d-galactopyranosyl-(1,6)-α-d-galactopyranoside in 26-57% yields against only 22% when native AgaB was used. It is interesting to note that the best variant was obtained by mutating a second-shell residue, with no direct interaction with the substrate or a catalytic amino acid. As this approach has proved to be efficient with both α- and β-glycosidases, it is a promising route to convert retaining glycosidases into transglycosidases.
2020
Sanejouand, Yves-Henri
A framework for the next generation of stationary cosmological models Divers
arxiv:2005.07931, 2020, (working paper or preprint).
@misc{sanejouand2020framework,
title = {A framework for the next generation of stationary cosmological models},
author = {Yves-Henri Sanejouand},
url = {https://arxiv.org/abs/2005.07931},
year = {2020},
date = {2020-12-28},
abstract = {According to a tired-light cosmological model where H(z) = H(0) (1 + z), the number density of galaxies has been nearly constant over the last 10 Gyr, at least, meaning that, as far as galaxies are concerned, the Universe has been stationary. On the other hand, an analysis of the luminosity distances of quasars and supernovae Ia shows that the Universe is far from being as transparent as assumed nowadays, the photon lifetime along the line-of-sight being one third of the Hubble time. The tired-light model advocated in the present study would be falsified if, for instance, the time-dilation of remote events were shown to have a general character, that is, if it were observed for phenomenons other than the light-curves of supernovae Ia.},
howpublished = {arxiv:2005.07931},
note = {working paper or preprint},
keywords = {},
pubstate = {published},
tppubtype = {misc}
}
According to a tired-light cosmological model where H(z) = H(0) (1 + z), the number density of galaxies has been nearly constant over the last 10 Gyr, at least, meaning that, as far as galaxies are concerned, the Universe has been stationary. On the other hand, an analysis of the luminosity distances of quasars and supernovae Ia shows that the Universe is far from being as transparent as assumed nowadays, the photon lifetime along the line-of-sight being one third of the Hubble time. The tired-light model advocated in the present study would be falsified if, for instance, the time-dilation of remote events were shown to have a general character, that is, if it were observed for phenomenons other than the light-curves of supernovae Ia.
2019
Sanejouand, Yves-Henri
A loss of photons along the line-of-sight can explain the Hubble diagram for quasars Non publié
2019, (working paper or preprint).
@unpublished{sanejouand:hal-02190771,
title = {A loss of photons along the line-of-sight can explain the Hubble diagram for quasars},
author = {Yves-Henri Sanejouand},
url = {https://hal.archives-ouvertes.fr/hal-02190771},
year = {2019},
date = {2019-01-01},
abstract = {In order to explain the Hubble diagram for quasars, an alternative to ΛCDM is proposed, namely, a simple Newtonian cosmological model where the loss of photons along the line-of-sight mimics the cosmic distance-duality relation, up to z ≈ 0.2. According to this model, after ≈ 3 Gyr of travel, half of the photons emitted by a galaxy have been lost.
},
note = {working paper or preprint},
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pubstate = {published},
tppubtype = {unpublished}
}
In order to explain the Hubble diagram for quasars, an alternative to ΛCDM is proposed, namely, a simple Newtonian cosmological model where the loss of photons along the line-of-sight mimics the cosmic distance-duality relation, up to z ≈ 0.2. According to this model, after ≈ 3 Gyr of travel, half of the photons emitted by a galaxy have been lost.
Sanejouand, Yves-Henri
No obvious change in the number density of galaxies up to z≈3.5 Divers
HAL, 2019, (working paper or preprint).
@misc{sanejouand:hal-02019920,
title = {No obvious change in the number density of galaxies up to z≈3.5},
author = {Yves-Henri Sanejouand},
url = {https://hal.archives-ouvertes.fr/hal-02019920},
year = {2019},
date = {2019-01-01},
abstract = {The analysis of the cumulative count of sources of gamma-ray bursts as a function of their redshift strongly suggests that the number density of star-forming galaxies is roughly constant, up to z ≈ 3.5. The analysis of the cumulative count of galaxies in the Hubble Ultra Deep Field further shows that the overall number density of galaxies is constant as well, up to z ≈ 2 at least. Since ΛCDM does not seem able to cope with the age of old objects, both analyses were performed using a non-standard redshift-distance relationship.},
howpublished = {HAL},
note = {working paper or preprint},
keywords = {},
pubstate = {published},
tppubtype = {misc}
}
The analysis of the cumulative count of sources of gamma-ray bursts as a function of their redshift strongly suggests that the number density of star-forming galaxies is roughly constant, up to z ≈ 3.5. The analysis of the cumulative count of galaxies in the Hubble Ultra Deep Field further shows that the overall number density of galaxies is constant as well, up to z ≈ 2 at least. Since ΛCDM does not seem able to cope with the age of old objects, both analyses were performed using a non-standard redshift-distance relationship.
2018
Sanejouand, Yves-Henri
Has the density of sources of gamma-ray burts been constant over the last ten billion years ? Article de journal
Dans: arXiv:1803.05303, 2018.
@article{sanejouand2018density,
title = {Has the density of sources of gamma-ray burts been constant over the last ten billion years ?},
author = {Yves-Henri Sanejouand},
url = {https://arxiv.org/abs/1803.05303},
year = {2018},
date = {2018-01-01},
journal = {arXiv:1803.05303},
abstract = {A generic tired-light mechanism is examined in which a photon, like any particle moving in a medium, experiences friction, that is, a force resisting its motion. If the velocity of light is assumed to be constant, this hypothesis yields a Hubble-like law which is also a consequence of the Rh = ct cosmology. Herein, it is used for estimating matter density as a function of redshift, allowing to show that the density of sources of long gamma-ray bursts appears to be nearly constant, up to z ≈ 4. Assuming that the later is a fair probe of the former, this means that matter density has been roughly constant over the last ten billion years, implying that, at least over this period, matter has been in an overall state of equilibrium.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
A generic tired-light mechanism is examined in which a photon, like any particle moving in a medium, experiences friction, that is, a force resisting its motion. If the velocity of light is assumed to be constant, this hypothesis yields a Hubble-like law which is also a consequence of the Rh = ct cosmology. Herein, it is used for estimating matter density as a function of redshift, allowing to show that the density of sources of long gamma-ray bursts appears to be nearly constant, up to z ≈ 4. Assuming that the later is a fair probe of the former, this means that matter density has been roughly constant over the last ten billion years, implying that, at least over this period, matter has been in an overall state of equilibrium.
2015
Sanejouand, Yves-Henri
A simple Hubble-like law in lieu of dark energy Divers
arXiv:1401.2919, 2015.
@misc{sanejouand2015simple,
title = {A simple Hubble-like law in lieu of dark energy},
author = {Yves-Henri Sanejouand},
url = {https://arxiv.org/abs/1401.2919},
year = {2015},
date = {2015-11-11},
abstract = {Within the frame of the Λ cold dark matter paradigm, a dark energy component of unknown origin is expected to represent nearly 70% of the energy of the Universe. Herein, a non-standard form of the Hubble law is advocated, with the aim of providing safe grounds on which alternative cosmologies could be developed. Noteworthy, it yields an age-redshift relationship which is consistent with available data. Together with a straightforward analysis of gamma-ray burst counts, it further suggests that the observable Universe has been euclidean and static over the last 12 Gyr. Although a non-standard distance-duality relation is then required for interpreting luminosity distances, the magnitude-redshift relationship obtained is compatible with type Ia supernovae data.},
howpublished = {arXiv:1401.2919},
keywords = {},
pubstate = {published},
tppubtype = {misc}
}
Within the frame of the Λ cold dark matter paradigm, a dark energy component of unknown origin is expected to represent nearly 70% of the energy of the Universe. Herein, a non-standard form of the Hubble law is advocated, with the aim of providing safe grounds on which alternative cosmologies could be developed. Noteworthy, it yields an age-redshift relationship which is consistent with available data. Together with a straightforward analysis of gamma-ray burst counts, it further suggests that the observable Universe has been euclidean and static over the last 12 Gyr. Although a non-standard distance-duality relation is then required for interpreting luminosity distances, the magnitude-redshift relationship obtained is compatible with type Ia supernovae data.
2014
Teze, David; Hendrickx, Johann; Czjzek, Mirjam; Ropartz, David; Sanejouand, Yves-Henri; Tran, Vinh; Tellier, Charles; Dion, Michel
Semi-rational approach for converting a GH1 ß-glycosidase into a ß-transglycosidase Article de journal
Dans: Protein Engineering, Design & Selection, vol. 27, no. 1, p. 13–19, 2014.
@article{teze2014semi,
title = {Semi-rational approach for converting a GH1 ß-glycosidase into a ß-transglycosidase},
author = {David Teze and Johann Hendrickx and Mirjam Czjzek and David Ropartz and Yves-Henri Sanejouand and Vinh Tran and Charles Tellier and Michel Dion},
doi = {10.1093/protein/gzt057},
year = {2014},
date = {2014-01-01},
urldate = {2014-01-01},
journal = {Protein Engineering, Design & Selection},
volume = {27},
number = {1},
pages = {13--19},
publisher = {Oxford University Press},
abstract = {A large number of retaining glycosidases catalyze both hydrolysis and transglycosylation reactions, but little is known about what determines the balance between these two activities (transglycosylation/hydrolysis ratio). We previously obtained by directed evolution the mutants F401S and N282T of Thermus thermophilus β-glycosidase (Ttβ-gly, glycoside hydrolase family 1 (GH1)), which display a higher transglycosylation/hydrolysis ratio than the wild-type enzyme. In order to find the cause of these activity modifications, and thereby set up a generic method for easily obtaining transglycosidases from glycosidases, we determined their X-ray structure. No major structural changes could be observed which could help to rationalize the mutagenesis of glycosidases into transglycosidases. However, as these mutations are highly conserved in GH1 β-glycosidases and are located around the −1 site, we pursued the isolation of new transglycosidases by targeting highly conserved amino acids located around the active site. Thus, by single-point mutagenesis on Ttβ-gly, we created four new mutants that exhibit improved synthetic activity, producing disaccharides in yields of 68–90% against only 36% when native Ttβ-gly was used. As all of the chosen positions were well conserved among GH1 enzymes, this approach is most probably a general route to convert GH1 glycosidases into transglycosidases.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
A large number of retaining glycosidases catalyze both hydrolysis and transglycosylation reactions, but little is known about what determines the balance between these two activities (transglycosylation/hydrolysis ratio). We previously obtained by directed evolution the mutants F401S and N282T of Thermus thermophilus β-glycosidase (Ttβ-gly, glycoside hydrolase family 1 (GH1)), which display a higher transglycosylation/hydrolysis ratio than the wild-type enzyme. In order to find the cause of these activity modifications, and thereby set up a generic method for easily obtaining transglycosidases from glycosidases, we determined their X-ray structure. No major structural changes could be observed which could help to rationalize the mutagenesis of glycosidases into transglycosidases. However, as these mutations are highly conserved in GH1 β-glycosidases and are located around the −1 site, we pursued the isolation of new transglycosidases by targeting highly conserved amino acids located around the active site. Thus, by single-point mutagenesis on Ttβ-gly, we created four new mutants that exhibit improved synthetic activity, producing disaccharides in yields of 68–90% against only 36% when native Ttβ-gly was used. As all of the chosen positions were well conserved among GH1 enzymes, this approach is most probably a general route to convert GH1 glycosidases into transglycosidases.