4O3F

Crystal Structure of mouse PGK1 3PG and terazosin(TZN) ternary complex

4O3F の概要

• エントリーDOI: 10.2210/pdb4o3f/pdb
• 関連するPDBエントリー: 4O33
• 分子名称: Phosphoglycerate kinase 1, [4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl][(2R)-tetrahydrofuran-2-yl]methanone, 3-PHOSPHOGLYCERIC ACID, ... (4 entities in total)
• 機能のキーワード: enzyme-drug complex, transferase-transferase activator complex, transferase/transferase activator
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Cytoplasm : P09411
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 45180.89

構造登録者

Li, X.L.,Finci, I.L.,Wang, J.H. (登録日: 2013-12-18, 公開日: 2014-10-29, 最終更新日: 2023-09-20)

主引用文献

Chen, X.,Zhao, C.,Li, X.,Wang, T.,Li, Y.,Cao, C.,Ding, Y.,Dong, M.,Finci, L.,Wang, J.H.,Li, X.,Liu, L.
Terazosin activates Pgk1 and Hsp90 to promote stress resistance.
Nat.Chem.Biol., 11:19-25, 2015

PubMed Abstract: Drugs that can protect against organ damage are urgently needed, especially for diseases such as sepsis and brain stroke. We discovered that terazosin (TZ), a widely marketed α1-adrenergic receptor antagonist, alleviated organ damage and improved survival in rodent models of stroke and sepsis. Through combined studies of enzymology and X-ray crystallography, we discovered that TZ binds a new target, phosphoglycerate kinase 1 (Pgk1), and activates its enzymatic activity, probably through 2,4-diamino-6,7-dimethoxyisoquinoline's ability to promote ATP release from Pgk1. Mechanistically, the ATP generated from Pgk1 may enhance the chaperone activity of Hsp90, an ATPase known to associate with Pgk1. Upon activation, Hsp90 promotes multistress resistance. Our studies demonstrate that TZ has a new protein target, Pgk1, and reveal its corresponding biological effect. As a clinical drug, TZ may be quickly translated into treatments for diseases including stroke and sepsis.

PubMed: 25383758
DOI: 10.1038/nchembio.1657

実験手法

X-RAY DIFFRACTION (2.106 Å)