4v28 | pdb_00004v28

Structure of an E333Q variant of the GH99 endo-alpha-mannanase from Bacteroides xylanisolvens in complex with Man-Man-Methylumbelliferone

spinqualitylabelsall models 4v28, resolution 1.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4v28 is a 1 chain structure with sequence from Bacteroides xylanisolvens XB1A. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.2Å Ligands: 4MU, ACT, EDO, MAN, PRD_900112 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function D6D1V7_9BACE Publication Abstract from PubMed Glycoside hydrolase family 99 (GH99) was created to categorize sequence-related glycosidases possessing endo-alpha-mannosidase activity: the cleavage of mannosidic linkages within eukaryotic N-glycan precursors (Glc1-3 Man9 GlcNAc2 ), releasing mono-, di- and triglucosylated-mannose (Glc1-3 -1,3-Man). GH99 family members have recently been implicated in the ability of Bacteroides spp., present within the gut microbiota, to metabolize fungal cell wall alpha-mannans, releasing alpha-1,3-mannobiose by hydrolysing alphaMan-1,3-alphaMan-->1,2-alphaMan-1,2-alphaMan sequences within branches off the main alpha-1,6-mannan backbone. We report the development of a series of substrates and inhibitors, which we use to kinetically and structurally characterise this novel endo-alpha-1,2-mannanase activity of bacterial GH99 enzymes from Bacteroides thetaiotaomicron and xylanisolvens. These data reveal an approximate 5 kJ mol-1 preference for mannose-configured substrates in the -2 subsite (relative to glucose), which inspired the development of a new inhibitor, alpha-mannopyranosyl-1,3-isofagomine (ManIFG), the most potent (bacterial) GH99 inhibitor reported to date. X-ray structures of ManIFG or a substrate in complex with wild-type or inactive mutants, respectively, of B. xylanisolvens GH99 reveal the structural basis for binding to D-mannose- rather than D-glucose-configured substrates. Structural and Kinetic Dissection of the endo-alpha-1,2-Mannanase Activity of Bacterial GH99 Glycoside Hydrolases from Bacteroides spp.,Hakki Z, Thompson AJ, Bellmaine S, Speciale G, Davies GJ, Williams SJ Chemistry. 2014 Dec 8. doi: 10.1002/chem.201405539. PMID:25487964 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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