1F5K

UROKINASE PLASMINOGEN ACTIVATOR B-CHAIN-BENZAMIDINE COMPLEX

1F5K の概要

• エントリーDOI: 10.2210/pdb1f5k/pdb
• 関連するPDBエントリー: 1EJN 1F5L 1F92
• 分子名称: UROKINASE-TYPE PLASMINOGEN ACTIVATOR, SULFATE ION, BENZAMIDINE, ... (4 entities in total)
• 機能のキーワード: urokinase, inhibitor, serine protease, human, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 28756.62

構造登録者

Zeslawska, E.,Schweinitz, A.,Karcher, A.,Sondermann, P.,Sperl, S.,Sturzebecher, J.,Jacob, U. (登録日: 2000-06-15, 公開日: 2001-06-15, 最終更新日: 2021-11-03)

主引用文献

Zeslawska, E.,Schweinitz, A.,Karcher, A.,Sondermann, P.,Sperl, S.,Sturzebecher, J.,Jacob, U.
Crystals of the urokinase type plasminogen activator variant beta(c)-uPAin complex with small molecule inhibitors open the way towards structure-based drug design.
J.Mol.Biol., 301:465-475, 2000

PubMed Abstract: Urokinase is a serine protease involved in cancer growth and metastasis. Here we present the first urokinase crystal structure in complex with reversible inhibitors at 2.1 and 2.6 A resolution. These inhibitor complex structures have been obtained from crystals of engineered urokinase type plasminogen activator designed to obtain a crystal form open for inhibitor soaking. The mutant C122S loses its flexible A-chain upon activation cleavage and crystallizes in the presence of benzamidine, which was later displaced by the desired inhibitor. This new soakable crystal form turned out to be of great value in the process of structure-based drug design. The evaluated binding mode of amiloride, and UKI-1D revealed a new subsite of the primary specificity pocket of urokinase that will be employed in the future ligand optimisation process.

PubMed: 10926521
DOI: 10.1006/jmbi.2000.3966

実験手法

X-RAY DIFFRACTION (1.8 Å)