4GQR
Human Pancreatic alpha-amylase in complex with myricetin
Summary for 4GQR
| Entry DOI | 10.2210/pdb4gqr/pdb |
| Related | 1BSI 1CPU 1HNY 3IJ7 3IJ8 4GQQ |
| Descriptor | Pancreatic alpha-amylase, 2-acetamido-2-deoxy-beta-D-glucopyranose, CALCIUM ION, ... (6 entities in total) |
| Functional Keywords | glycosyl hydrolase, diabetes, obesity, digestion, glycosidase, enzyme inhibition, flavonol, drug design, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Secreted, extracellular space: P04746 |
| Total number of polymer chains | 1 |
| Total formula weight | 56546.28 |
| Authors | Williams, L.K.,Brayer, G.D. (deposition date: 2012-08-23, release date: 2012-10-24, Last modification date: 2020-07-29) |
| Primary citation | Williams, L.K.,Li, C.,Withers, S.G.,Brayer, G.D. Order and disorder: differential structural impacts of myricetin and ethyl caffeate on human amylase, an antidiabetic target. J.Med.Chem., 55:10177-10186, 2012 Cited by PubMed Abstract: The increasing prevalence of diabetes has accelerated the search for new drugs derived from natural sources. To define the functional features of two such families of compounds, the flavonols and the ethyl caffeates, we have determined the high-resolution structures of representative inhibitors in complex with human pancreatic α-amylase. Myricetin binds at the active site and interacts directly with the catalytic residues despite its bulky planar nature. Notably, it reduces the normal conformational flexibility of the adjacent substrate binding cleft. In contrast, bound ethyl caffeate acts by disordering precisely those polypeptide chain segments that make up the active site binding cleft. It also operates from binding sites far removed from the active site, a property not observed in any other class of human α-amylase inhibitor studied to date. Given the current inadequacy of drugs directed at diabetes, the use of optimized flavonols and ethyl caffeates may present an alternative therapeutic route. PubMed: 23050660DOI: 10.1021/jm301273u PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.2 Å) |
Structure validation
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