@article{Teze2020,

title = {A Single Point Mutation Converts GH84 O-GlcNAc Hydrolases into Phosphorylases: Experimental and Theoretical Evidence},

author = {David Teze and Joan Coines and Lluís Raich and Valentina Kalichuk and Claude Solleux and Charles Tellier and Corinne André-Miral and Birte Svensson and Carme Rovira},

doi = {10.1021/jacs.9b09655},

issn = {15205126},

year  = {2020},

date = {2020-01-01},

journal = {Journal of the American Chemical Society},

volume = {142},

number = {5},

pages = {2120--2124},

abstract = {Glycoside hydrolases and phosphorylases are two major classes of enzymes responsible for the cleavage of glycosidic bonds. Here we show that two GH84 O-GlcNAcase enzymes can be converted to efficient phosphorylases by a single point mutation. Noteworthy, the mutated enzymes are over 10-fold more active than naturally occurring glucosaminide phosphorylases. We rationalize this novel transformation using molecular dynamics and QM/MM metadynamics methods, showing that the mutation changes the electrostatic potential at the active site and reduces the energy barrier for phosphorolysis by 10 kcaltextperiodcenteredmol-1. In addition, the simulations unambiguously reveal the nature of the intermediate as a glucose oxazolinium ion, clarifying the debate on the nature of such a reaction intermediate in glycoside hydrolases operating via substrate-assisted catalysis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{10.3389/fnagi.2020.00103,

title = {Resveratrol Derivatives as Potential Treatments for Alzheimer’s and Parkinson’s Disease},

author = {Bruno Dutra Arbo and Corinne André-Miral and Raif Gregorio Nasre-Nasser and Lúcia Emanueli Schimith and Michele Goulart Santos and Dennis Costa-Silva and Ana Luiza Muccillo-Baisch and Mariana Appel Hort},

url = {https://www.frontiersin.org/article/10.3389/fnagi.2020.00103},

doi = {10.3389/fnagi.2020.00103},

issn = {1663-4365},

year  = {2020},

date = {2020-01-01},

journal = {Frontiers in Aging Neuroscience},

volume = {12},

pages = {103},

abstract = {Neurodegenerative diseases are characterized by the progressive loss of neurons in different regions of the nervous system. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most prevalent neurodegenerative diseases, and the symptoms associated with these pathologies are closely related to the regions that are most affected by the process of neurodegeneration. Despite their high prevalence, currently, there is no cure or disease-modifying drugs for the treatment of these conditions. In the last decades, due to the need for the development of new treatments for neurodegenerative diseases, several authors have investigated the neuroprotective actions of naturally occurring molecules, such as resveratrol. Resveratrol is a stilbene found in several plants, including grapes, blueberries, raspberries, and peanuts. Studies have shown that resveratrol presents neuroprotective actions in experimental models of AD and PD, however, its clinical application is limited due to its rapid metabolism and low bioavailability. In this context, studies have proposed that structural changes in the resveratrol molecule, including glycosylation, alkylation, halogenation, hydroxylation, methylation, and prenylation could lead to the development of derivatives with enhanced bioavailability and pharmacological activity. Therefore, this review article aims to discuss how resveratrol derivatives could represent viable molecules in the search for new drugs for the treatment of AD and PD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Visnapuu2020,

title = {Identification and characterization of a β-n-acetylhexosaminidase with a biosynthetic activity from the marine bacterium paraglaciecola hydrolytica S66T},

author = {Triinu Visnapuu and David Teze and Christian Kjeldsen and Aleksander Lie and Jens Øllgaard Duus and Corinne André-Miral and Lars Haastrup Pedersen and Peter Stougaard and Birte Svensson},

doi = {10.3390/ijms21020417},

issn = {14220067},

year  = {2020},

date = {2020-01-01},

journal = {International Journal of Molecular Sciences},

volume = {21},

number = {2},

publisher = {MDPI AG},

abstract = {β-N-Acetylhexosaminidases are glycoside hydrolases (GHs) acting on N-acetylated carbohydrates and glycoproteins with the release of N-acetylhexosamines. Members of the family GH20 have been reported to catalyze the transfer of N-acetylglucosamine (GlcNAc) to an acceptor, i.e., the reverse of hydrolysis, thus representing an alternative to chemical oligosaccharide synthesis. Two putative GH20 β-N-acetylhexosaminidases, PhNah20A and PhNah20B, encoded by the marine bacterium Paraglaciecola hydrolytica S66T, are distantly related to previously characterized enzymes. Remarkably, PhNah20A was located by phylogenetic analysis outside clusters of other studied β-N-acetylhexosaminidases, in a unique position between bacterial and eukaryotic enzymes. We successfully produced recombinant PhNah20A showing optimum activity at pH 6.0 and 50◦C, hydrolysis of GlcNAc β-1,4 and β-1,3 linkages in chitobiose (GlcNAc)2 and GlcNAc-1,3-β-Gal-1,4-β-Glc (LNT2), a human milk oligosaccharide core structure. The kinetic parameters of PhNah20A for p-nitrophenyl-GlcNAc and p-nitrophenyl-GalNAc were highly similar: kcat /KM being 341 and 344 mM−1 s−1, respectively. PhNah20A was unstable in dilute solution, but retained full activity in the presence of 0.5% bovine serum albumin (BSA). PhNah20A catalyzed the formation of LNT2, the non-reducing trisaccharide β-Gal-1,4-β-Glc-1,1-β-GlcNAc, and in low amounts the β-1,2-or β-1,3-linked trisaccharide β-Gal-1,4(β-GlcNAc)-1,x-Glc by a transglycosylation of lactose using 2-methyl-(1,2-dideoxy-α-d-glucopyrano)-oxazoline (NAG-oxazoline) as the donor. PhNah20A is the first characterized member of a distinct subgroup within GH20 β-N-acetylhexosaminidases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Andre-Miral2015,

title = {De novo design of a trans-β-N-acetylglucosaminidase activity from a GH1 β-glycosidase by mechanism engineering},

author = {Corinne André-Miral and Fankroma Mt Koné and Claude Solleux and Cyrille Grandjean and Michel Dion and Vinh Tran and Charles Tellier},

doi = {10.1093/glycob/cwu121},

issn = {14602423},

year  = {2015},

date = {2015-01-01},

journal = {Glycobiology},

volume = {25},

number = {4},

pages = {394--402},

abstract = {Glycoside hydrolases are particularly abundant in all areas of metabolism as they are involved in the degradation of natural polysaccharides and glycoconjugates. These enzymes are classified into 133 families (CAZy server, http://www.cazy.org) in which members of each family have a similar structure and catalytic mechanism. In order to understand better the structure/function relationships of these enzymes and their evolution and to develop new robust evolved glycosidases, we undertook to convert a Family 1 thermostable β-glycosidase into an exo-β-N-acetylglucosaminidase. This latter activity is totally absent in Family 1, while natural β-hexosaminidases belong to CAZy Families 3, 20 and 84. Using molecular modeling, we first showed that the docking of N-acetyl-d-glucosamine in the subsite -1 of the β-glycosidase from Thermus thermophilus (TtβGly) suggested several steric conflicts with active site amino-acids (N163, E338) induced by the N-acetyl group. Both N163A and N163D-E338G mutations induced significant N-acetylglucosaminidase activity in TtβGly. The double mutant N163D-E338G was also active on the bicyclic oxazoline substrate, suggesting that this mutated enzyme uses a catalytic mechanism involving a substrate-assisted catalysis with a noncovalent oxazoline intermediate, similar to the N-acetylglucosaminidases from Families 20 and 84. Furthermore, a very efficient trans-N-acetylglucosaminidase activity was observed when the double mutant was incubated in the presence of NAG-oxazoline as a donor and N-methyl-O-benzyl-N-(β-d-glucopyranosyl)-hydroxylamine as an acceptor. More generally, this work demonstrates that it is possible to exchange the specificities and catalytic mechanisms with minimal changes between phylogenetically distant protein structures.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}