4DVA

The crystal structure of human urokinase-type plasminogen activator catalytic domain

4DVA の概要

• エントリーDOI: 10.2210/pdb4dva/pdb
• 関連するPDBエントリー: 2NWN 4DVB 4DW2
• 分子名称: Urokinase-type plasminogen activator, SULFATE ION, HEXAETHYLENE GLYCOL, ... (4 entities in total)
• 機能のキーワード: hydrolase, plasminogen activation, protease, serine protease
• 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: 28472.39

構造登録者

Jiang, L.,Botkjaer, K.A.,Andersen, L.M.,Yuan, C.,Andreasen, P.A.,Huang, M. (登録日: 2012-02-23, 公開日: 2013-01-16, 最終更新日: 2024-11-20)

主引用文献

Jiang, L.,Botkjaer, K.A.,Andersen, L.M.,Yuan, C.,Andreasen, P.A.,Huang, M.
Rezymogenation of active urokinase induced by an inhibitory antibody
Biochem.J., 449:161-166, 2013

PubMed Abstract: An important regulatory mechanism of serine proteases is the proteolytic conversion of the inactive pro-enzyme, or zymogen, into the active enzyme. This activation process is generally considered an irreversible process. In the present study, we demonstrate that an active enzyme can be converted back into its zymogen form. We determined the crystal structure of uPA (urokinase-type plasminogen activator) in complex with an inhibitory antibody, revealing that the antibody 'rezymogenizes' already activated uPA. The present study demonstrates a new regulatory mechanism of protease activity, which is also an extreme case of protein allostery. Mechanistically, the antibody binds a single surface-exposed loop, named the autolysis loop, thereby preventing the stabilization of uPA in its active conformation. We argue that this autolysis loop is a key structural element for rezymogenation of other proteases, and will be a new target site for pharmacological intervention with serine protease activity.

PubMed: 23016918
DOI: 10.1042/BJ20121132

実験手法

X-RAY DIFFRACTION (1.94 Å)