1GJ4

SELECTIVITY AT S1, H2O DISPLACEMENT, UPA, TPA, SER190/ALA190 PROTEASE, STRUCTURE-BASED DRUG DESIGN

1GJ4 の概要

• エントリーDOI: 10.2210/pdb1gj4/pdb
• 関連するPDBエントリー: 1C5N
• 分子名称: THROMBIN, ACETYL HIRUDIN, SODIUM ION, ... (6 entities in total)
• 機能のキーワード: three-centered, very short hydrogen bond, oxyanion hole water, shift of pka of his57, structure-based drug design, specificity, urokinase, trypsin, thrombin, zn+2-mediated inhibition, blood clotting, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted, extracellular space: P00734 P00734; Secreted: P28504
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 35624.99

構造登録者

Katz, B.A.,Sprengeler, P.A.,Luong, C.,Verner, E.,Spencer, J.R.,Breitenbucher, J.G.,Hui, H.,McGee, D.,Allen, D.,Martelli, A.,Mackman, R.L. (登録日: 2001-04-27, 公開日: 2002-04-27, 最終更新日: 2024-10-30)

主引用文献

Katz, B.A.,Sprengeler, P.A.,Luong, C.,Verner, E.,Elrod, K.,Kirtley, M.,Janc, J.,Spencer, J.R.,Breitenbucher, J.G.,Hui, H.,McGee, D.,Allen, D.,Martelli, A.,Mackman, R.L.
Engineering inhibitors highly selective for the S1 sites of Ser190 trypsin-like serine protease drug targets.
Chem.Biol., 8:1107-1121, 2001

PubMed Abstract: Involved or implicated in a wide spectrum of diseases, trypsin-like serine proteases comprise well studied drug targets and anti-targets that can be subdivided into two major classes. In one class there is a serine at position 190 at the S1 site, as in urokinase type plasminogen activator (urokinase or uPA) and factor VIIa, and in the other there is an alanine at 190, as in tissue type plasminogen activator (tPA) and factor Xa. A hydrogen bond unique to Ser190 protease-arylamidine complexes between O gamma(Ser190) and the inhibitor amidine confers an intrinsic preference for such inhibitors toward Ser190 proteases over Ala190 counterparts.

PubMed: 11731301
DOI: 10.1016/S1074-5521(01)00084-9

実験手法

X-RAY DIFFRACTION (1.81 Å)