5XG4

Crystal structure of uPA in complex with quercetin

5XG4 の概要

• エントリーDOI: 10.2210/pdb5xg4/pdb
• 分子名称: Urokinase-type plasminogen activator, 3,5,7,3',4'-PENTAHYDROXYFLAVONE, 1-(2-METHOXY-ETHOXY)-2-{2-[2-(2-METHOXY-ETHOXY]-ETHOXY}-ETHANE, ... (4 entities in total)
• 機能のキーワード: serine proteases, upa, pepetide inhibitors, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Secreted: P00749
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 28284.17

構造登録者

Jiang, L.,Huang, M. (登録日: 2017-04-11, 公開日: 2017-07-26, 最終更新日: 2024-11-13)

主引用文献

Xue, G.,Gong, L.,Yuan, C.,Xu, M.,Wang, X.,Jiang, L.,Huang, M.
A structural mechanism of flavonoids in inhibiting serine proteases
Food Funct, 8:2437-2443, 2017

PubMed Abstract: Quercetin is a member of the flavonoids and was previously demonstrated to inhibit trypsin-like serine proteases at micromolar potencies. Different molecular models were proposed to explain such inhibition. However, controversies remain on the molecular details of inhibition. Here, we report the X-ray crystal structure of quercetin in a complex with the urokinase-type plasminogen activator (uPA), an archetypical serine protease. The structure showed that quercetin binds to the specific substrate binding pocket (S1 pocket) of uPA mainly through its two neighboring phenolic hydroxyl groups. Our study thus provides unambiguous evidence to support quercetin binding to serine proteases and defines the molecular basis of the interaction. Our results further establish that natural products with two adjacent phenolic hydroxyl groups (or catechol) are likely to inhibit other trypsin-like serine proteases, a new mechanism formerly under-recognized.

PubMed: 28644504
DOI: 10.1039/c6fo01825d

実験手法

X-RAY DIFFRACTION (3 Å)