4udk

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== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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To metabolize both dietary fiber constituent carbohydrates and host glycans lining the intestinal epithelium, gut bacteria produce a wide range of carbohydrate-active enzymes, of which glycoside hydrolases are the main components. In this study, we describe the ability of phosphorylases to participate in the breakdown of human N-glycans, from an analysis of the substrate specificity of UhgbMP, a mannoside phosphorylase of the GH130 protein family discovered by functional metagenomics. UhgbMP is found to phosphorolyze beta-D-Manp-1,4-beta-D-GlcpNAc-1,4-D-GlcpNAc and is also a highly efficient enzyme to catalyze the synthesis of this precious N-glycan core oligosaccharide by reverse phosphorolysis. Analysis of sequence conservation within family GH130, mapped on a three-dimensional model of UhgbMP and supported by site-directed mutagenesis results, revealed two GH130 subfamilies and allowed the identification of key residues responsible for catalysis and substrate specificity. The analysis of the genomic context of 65 known GH130 sequences belonging to human gut bacteria indicates that the enzymes of the GH130_1 subfamily would be involved in mannan catabolism, whereas the enzymes belonging to the GH130_2 subfamily would rather work in synergy with glycoside hydrolases of the GH92 and GH18 families in the breakdown of N-glycans. The use of GH130 inhibitors as therapeutic agents or functional foods could thus be considered as an innovative strategy to inhibit N-glycan degradation, with the ultimate goal of protecting, or restoring, the epithelial barrier.
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The first crystal structure of Uhgb_MP, a beta-1,4-mannopyranosyl-chitobiose phosphorylase belonging to the GH130 family which is involved in N-glycan degradation by human gut bacteria, was solved at 1.85 A resolution in the apo form and in complex with mannose and N-acetylglucosamine. SAXS and crystal structure analysis revealed a hexameric structure, a specific feature of GH130 enzymes among other glycoside phosphorylases. Mapping of the -1 and +1 subsites in the presence of phosphate confirmed the conserved Asp104 as the general acid/base catalytic residue, which is in agreement with a single-step reaction mechanism involving Man O3 assistance for proton transfer. Analysis of this structure, the first to be solved for a member of the GH130_2 subfamily, revealed Met67, Phe203 and the Gly121-Pro125 loop as the main determinants of the specificity of Uhgb_MP and its homologues towards the N-glycan core oligosaccharides and mannan, and the molecular bases of the key role played by GH130 enzymes in the catabolism of dietary fibre and host glycans.
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Role of glycoside phosphorylases in mannose foraging by human gut bacteria.,Ladeveze S, Tarquis L, Cecchini DA, Bercovici J, Andre I, Topham CM, Morel S, Laville E, Monsan P, Lombard V, Henrissat B, Potocki-Veronese G J Biol Chem. 2013 Nov 8;288(45):32370-83. doi: 10.1074/jbc.M113.483628. Epub 2013, Sep 16. PMID:24043624<ref>PMID:24043624</ref>
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Structural bases for N-glycan processing by mannoside phosphorylase.,Ladeveze S, Cioci G, Roblin P, Mourey L, Tranier S, Potocki-Veronese G Acta Crystallogr D Biol Crystallogr. 2015 Jun;71(Pt 6):1335-46. doi:, 10.1107/S1399004715006604. Epub 2015 May 14. PMID:26057673<ref>PMID:26057673</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

Revision as of 09:04, 17 June 2015

Crystal structure of b-1,4-mannopyranosyl-chitobiose phosphorylase at 1.76 Angstrom from unknown human gut bacteria (Uhgb_MP) in complex with N-acetyl-D-glucosamine, beta-D-mannopyranose and inorganic phosphate

4udk, resolution 1.76Å

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