4w93 | pdb_00004w93

Human pancreatic alpha-amylase in complex with montbretin A

spinqualitylabelsall models 4w93, resolution 1.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4w93 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 3L9, CA, CL, PCA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AMYP_HUMAN Publication Abstract from PubMed The complex plant flavonol glycoside montbretin A is a potent (Ki = 8 nM) and specific inhibitor of human pancreatic alpha-amylase with potential as a therapeutic for diabetes and obesity. Controlled degradation studies on montbretin A, coupled with inhibition analyses, identified an essential high-affinity core structure comprising the myricetin and caffeic acid moieties linked via a disaccharide. X-ray structural analyses of the montbretin A-human alpha-amylase complex confirmed the importance of this core structure and revealed a novel mode of glycosidase inhibition wherein internal pi-stacking interactions between the myricetin and caffeic acid organize their ring hydroxyls for optimal hydrogen bonding to the alpha-amylase catalytic residues D197 and E233. This novel inhibitory motif can be reproduced in a greatly simplified analog, offering potential for new strategies for glycosidase inhibition and therapeutic development. The amylase inhibitor montbretin A reveals a new glycosidase inhibition motif.,Williams LK, Zhang X, Caner S, Tysoe C, Nguyen NT, Wicki J, Williams DE, Coleman J, McNeill JH, Yuen V, Andersen RJ, Withers SG, Brayer GD Nat Chem Biol. 2015 Jul 27. doi: 10.1038/nchembio.1865. PMID:26214255 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Amylase 3D structures

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