1NU7

Staphylocoagulase-Thrombin Complex

1NU7 の概要

• エントリーDOI: 10.2210/pdb1nu7/pdb
• 関連するPDBエントリー: 1NU9
• 関連するBIRD辞書のPRD_ID: PRD_000377
• 分子名称: Thrombin light chain, Thrombin heavy chain, Staphylocoagulase, ... (7 entities in total)
• 機能のキーワード: thrombin non-proteolytic activator, hydrolase-hydrolase inhibitor complex, protein binding, hydrolase/hydrolase inhibitor
• 由来する生物種: Staphylococcus aureus; 詳細
• 細胞内の位置: Secreted, extracellular space: P00734 P00734
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 135045.67

構造登録者

Friedrich, R.,Bode, W.,Fuentes-Prior, P.,Panizzi, P.,Bock, P.E. (登録日: 2003-01-31, 公開日: 2003-10-07, 最終更新日: 2024-12-25)

主引用文献

Friedrich, R.,Panizzi, P.,Fuentes-Prior, P.,Richter, K.,Verhamme, I.,Anderson, P.J.,Kawabata, S.,Huber, R.,Bode, W.,Bock, P.E.
Staphylocoagulase is a prototype for the mechanism of cofactor-induced zymogen activation
NATURE, 425:535-539, 2003

PubMed Abstract: Many bacterial pathogens secrete proteins that activate host trypsinogen-like enzyme precursors, most notably the proenzymes of the blood coagulation and fibrinolysis systems. Staphylococcus aureus, an important human pathogen implicated in sepsis and endocarditis, secretes the cofactor staphylocoagulase, which activates prothrombin, without the usual proteolytic cleavages, to directly initiate blood clotting. Here we present the 2.2 A crystal structures of human alpha-thrombin and prethrombin-2 bound to a fully active staphylocoagulase variant. The cofactor consists of two domains, each with three-helix bundles; this is a novel fold that is distinct from known serine proteinase activators, particularly the streptococcal plasminogen activator streptokinase. The staphylocoagulase fold is conserved in other bacterial plasma-protein-binding factors and extracellular-matrix-binding factors. Kinetic studies confirm the importance of isoleucine 1 and valine 2 at the amino terminus of staphylocoagulase for zymogen activation. In addition to making contacts with the 148 loop and (pro)exosite I of prethrombin-2, staphylocoagulase inserts its N-terminal peptide into the activation pocket of bound prethrombin-2, allosterically inducing functional catalytic machinery. These investigations demonstrate unambiguously the validity of the zymogen-activation mechanism known as 'molecular sexuality'.

PubMed: 14523451
DOI: 10.1038/nature01962

実験手法

X-RAY DIFFRACTION (2.2 Å)