2WPI

factor IXa superactive double mutant

2WPI の概要

• エントリーDOI: 10.2210/pdb2wpi/pdb
• 関連するPDBエントリー: 1CFH 1CFI 1EDM 1IXA 1MGX 1NL0 1RFN 2WPH 2WPJ 2WPK 2WPL 2WPM
• 関連するBIRD辞書のPRD_ID: PRD_001148
• 分子名称: COAGULATION FACTOR IXA LIGHT CHAIN, D-PHE-PRO-ARG-CHLOROMETHYL KETONE, COAGULATION FACTOR IXA HEAVY CHAIN, ... (5 entities in total)
• 機能のキーワード: blood clotting, hydrolase, glycoprotein, hemostasis
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Secreted : P00740 P00740
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 33056.64

構造登録者

Zogg, T.,Brandstetter, H. (登録日: 2009-08-06, 公開日: 2009-12-22, 最終更新日: 2024-11-20)

主引用文献

Zogg, T.,Brandstetter, H.
Structural Basis of the Cofactor- and Substrate-Assisted Activation of Human Coagulation Factor Ixa
Structure, 17:1669-, 2009

PubMed Abstract: Human coagulation factor IX serves both to maintain and to control blood coagulation. The dual function of this hemophilic factor is implemented by a tiered activation mechanism. Processed two-chain factor IXa is catalytically silent; only together with its cofactor VIIIa does factor IXa form the highly potent Xase complex. The detailed mechanism of this secondary activation has remained elusive so far. Here we present the crystal structures of Xase-like factor IXa mutants with several-thousand-fold activity enhancement that mimic the secondary activation by Xase formation. The structures reveal how cofactor-triggered and substrate-assisted modulations in the factor IXa 99- and 60-loops cooperate in S4 through S2' formation, allowing for productive substrate recognition. We could further physically map and visualize a distinct communication line, along which agonists such as Ca(2+) direct their effects to the active site and vice versa.

PubMed: 20004170
DOI: 10.1016/J.STR.2009.10.011

実験手法

X-RAY DIFFRACTION (1.99 Å)