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PDBsum entry 4gqq

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Hydrolase/hydrolase inhibitor PDB id
4gqq
Jmol
Contents
Protein chain
496 a.a.
Ligands
NAG
0XR ×3
Metals
_CA
_CL
Waters ×240

References listed in PDB file
Key reference
Title Order and disorder: differential structural impacts of myricetin and ethyl caffeate on human amylase, An antidiabetic target.
Authors L.K.Williams, C.Li, S.G.Withers, G.D.Brayer.
Ref. J Med Chem, 2012, 55, 10177-10186.
PubMed id 23050660
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.
PROCHECK
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