3LU9

Crystal structure of human thrombin mutant S195A in complex with the extracellular fragment of human PAR1

3LU9 の概要

• エントリーDOI: 10.2210/pdb3lu9/pdb
• 関連するPDBエントリー: 1SHH
• 分子名称: Prothrombin, Proteinase-activated receptor 1, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: serine protease, acute phase, blood coagulation, calcium, cleavage on pair of basic residues, disease mutation, disulfide bond, gamma-carboxyglutamic acid, glycoprotein, hydrolase, kringle, pharmaceutical, polymorphism, protease, secreted, zymogen, cell membrane, g-protein coupled receptor, membrane, phosphoprotein, receptor, transducer, transmembrane
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 76841.28

構造登録者

Gandhi, P.S.,Chen, Z.,Di Cera, E. (登録日: 2010-02-17, 公開日: 2010-03-16, 最終更新日: 2024-11-06)

主引用文献

Gandhi, P.S.,Chen, Z.,Di Cera, E.
Crystal structure of thrombin bound to the uncleaved extracellular fragment of PAR1.
J.Biol.Chem., 285:15393-15398, 2010

PubMed Abstract: Abundant structural information exists on how thrombin recognizes ligands at the active site or at exosites separate from the active site region, but remarkably little is known about how thrombin recognizes substrates that bridge both the active site and exosite I. The case of the protease-activated receptor PAR1 is particularly relevant in view of the plethora of biological effects associated with its activation by thrombin. Here, we present the 1.8 A resolution structure of thrombin S195A in complex with a 30-residue long uncleaved extracellular fragment of PAR1 that documents for the first time a productive binding mode bridging the active site and exosite I. The structure reveals two unexpected features of the thrombin-PAR1 interaction. The acidic P3 residue of PAR1, Asp(39), does not hinder binding to the active site and actually makes favorable interactions with Gly(219) of thrombin. The tethered ligand domain shows a considerable degree of disorder even when bound to thrombin. The results fill a significant gap in our understanding of the molecular mechanisms of recognition by thrombin in ways that are relevant to other physiological substrates.

PubMed: 20236938
DOI: 10.1074/jbc.M110.115337

実験手法

X-RAY DIFFRACTION (1.8 Å)