4GQQ

Human pancreatic alpha-amylase with bound ethyl caffeate

4GQQ の概要

• エントリーDOI: 10.2210/pdb4gqq/pdb
• 関連するPDBエントリー: 1BSI 1CPU 1HNY 3IJ7 3IJ8 4GQR
• 分子名称: Pancreatic alpha-amylase, 2-acetamido-2-deoxy-beta-D-glucopyranose, ethyl (2E)-3-(3,4-dihydroxyphenyl)prop-2-enoate, ... (6 entities in total)
• 機能のキーワード: glycosyl hydrolase, noncompetitive inhibition, diabetes, obesity, digestion, glycosidase, enzyme inhibition, flavonol, myricetin, drug design, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted, extracellular space: P04746
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 56852.68

構造登録者

Williams, L.K.,Brayer, G.D. (登録日: 2012-08-23, 公開日: 2012-10-24, 最終更新日: 2024-11-27)

主引用文献

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

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: 23050660
DOI: 10.1021/jm301273u

実験手法

X-RAY DIFFRACTION (1.35 Å)