5JB9

Crystal structure of factor IXa K98T variant in complex with PPACK

5JB9 の概要

• エントリーDOI: 10.2210/pdb5jb9/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000020
• 分子名称: Coagulation factor IX, D-phenylalanyl-N-[(2S,3S)-6-{[amino(iminio)methyl]amino}-1-chloro-2-hydroxyhexan-3-yl]-L-prolinamide, CALCIUM ION, ... (6 entities in total)
• 機能のキーワード: blood clotting, hydrolase, glycoprotein, haemostasis
• 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: 2
• 化学式量合計: 33130.23

構造登録者

Kristensen, L.H.,Brandstetter, H. (登録日: 2016-04-13, 公開日: 2016-06-01, 最終更新日: 2024-11-13)

主引用文献

Kristensen, L.H.,Olsen, O.H.,Blouse, G.E.,Brandstetter, H.
Releasing the brakes in coagulation Factor IXa by co-operative maturation of the substrate-binding site.
Biochem.J., 473:2395-2411, 2016

PubMed Abstract: Coagulation Factor IX is positioned at the merging point of the intrinsic and extrinsic blood coagulation cascades. Factor IXa (activated Factor IX) serves as the trigger for amplification of coagulation through formation of the so-called Xase complex, which is a ternary complex of Factor IXa, its substrate Factor X and the cofactor Factor VIIIa on the surface of activated platelets. Within the Xase complex the substrate turnover by Factor IXa is enhanced 200000-fold; however, the mechanistic and structural basis for this dramatic enhancement remains only partly understood. A multifaceted approach using enzymatic, biophysical and crystallographic methods to evaluate a key set of activity-enhanced Factor IXa variants has demonstrated a delicately balanced bidirectional network. Essential molecular interactions across multiple regions of the Factor IXa molecule co-operate in the maturation of the active site. This maturation is specifically facilitated by long-range communication through the Ile(212)-Ile(213) motif unique to Factor IXa and a flexibility of the 170-loop that is further dependent on the conformation in the Cys(168)-Cys(182) disulfide bond. Ultimately, the network consists of compensatory brakes (Val(16) and Ile(213)) and accelerators (Tyr(99) and Phe(174)) that together allow for a subtle fine-tuning of enzymatic activity.

PubMed: 27208168
DOI: 10.1042/BCJ20160336

実験手法

X-RAY DIFFRACTION (1.3 Å)