4d4b

The catalytic domain, BcGH76, of Bacillus circulans Aman6 in complex with MSMSMe

spinqualitylabelsall models 4d4b, resolution 1.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4d4b is a 2 chain structure with sequence from Niallia circulans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EDO, MAN, MSX Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [Q9Z4P9_NIACI] Publication Abstract from PubMed alpha-Mannosidases and alpha-mannanases have attracted attention for the insight they provide into nucleophilic substitution at the hindered anomeric center of alpha-mannosides, and the potential of mannosidase inhibitors as cellular probes and therapeutic agents. We report the conformational itinerary of the family GH76 alpha-mannanases studied through structural analysis of the Michaelis complex and synthesis and evaluation of novel aza/imino sugar inhibitors. A Michaelis complex in an O S2 conformation, coupled with distortion of an azasugar in an inhibitor complex to a high energy B2,5 conformation are rationalized through ab initio QM/MM metadynamics that show how the enzyme surface restricts the conformational landscape of the substrate, rendering the B2,5 conformation the most energetically stable on-enzyme. We conclude that GH76 enzymes perform catalysis using an itinerary that passes through O S2 and B2,5 not equal conformations, information that should inspire the development of new antifungal agents. Evidence for a Boat Conformation at the Transition State of GH76 alpha-1,6-Mannanases-Key Enzymes in Bacterial and Fungal Mannoprotein Metabolism.,Thompson AJ, Speciale G, Iglesias-Fernandez J, Hakki Z, Belz T, Cartmell A, Spears RJ, Chandler E, Temple MJ, Stepper J, Gilbert HJ, Rovira C, Williams SJ, Davies GJ Angew Chem Int Ed Engl. 2015 Mar 13. doi: 10.1002/anie.201410502. PMID:25772148 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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