1FPH

THE INTERACTION OF THROMBIN WITH FIBRINOGEN: A STRUCTURAL BASIS FOR ITS SPECIFICITY

1FPH の概要

• エントリーDOI: 10.2210/pdb1fph/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000379
• 分子名称: ALPHA-THROMBIN (SMALL SUBUNIT), ALPHA-THROMBIN (LARGE SUBUNIT), HIRUDIN, ... (5 entities in total)
• 機能のキーワード: hydrolase, serine proteinase, 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
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 36426.90

構造登録者

Stubbs, M.T.,Bode, W. (登録日: 1993-04-21, 公開日: 1994-01-31, 最終更新日: 2024-10-09)

主引用文献

Stubbs, M.T.,Oschkinat, H.,Mayr, I.,Huber, R.,Angliker, H.,Stone, S.R.,Bode, W.
The interaction of thrombin with fibrinogen. A structural basis for its specificity.
Eur.J.Biochem., 206:187-195, 1992

PubMed Abstract: The structure of the ternary complex of human alpha-thrombin with a covalently bound analogue of fibrinopeptide A and a C-terminal hirudin peptide has been determined by X-ray diffraction methods at 0.25 nm resolution. Fibrinopeptide A folds in a compact manner, bringing together hydrophobic residues that slot into the apolar binding site of human alpha-thrombin. Fibrinogen residue Phe8 occupies the aryl-binding site of thrombin, adjacent to fibrinogen residues Leu9 and Val15 in the S2 subsite. The species diversity of fibrinopeptide A is analysed with respect to its conformation and its interaction with thrombin. The non-covalently attached peptide fragment hirudin(54-65) exhibits an identical conformation to that observed in the hirudin-thrombin complex. The occupancy of the secondary fibrinogen-recognition exosite by this peptide imposes restrictions on the manner of fibrinogen binding. The surface topology of the thrombin molecule indicates positions P1'-P3', differ from those of the canonical serine-proteinase inhibitors, suggesting a mechanical model for the switching of thrombin activity from fibrinogen cleavage to protein-C activation on thrombomodulin complex formation. The multiple interactions between thrombin and fibrinogen provide an explanation for the narrow specificity of thrombin. Structural grounds can be put forward for certain congenital clotting disorders.

PubMed: 1587268
DOI: 10.1111/j.1432-1033.1992.tb16916.x

実験手法

X-RAY DIFFRACTION (2.5 Å)