Loading
PDBj
MenuPDBj@FacebookPDBj@TwitterPDBj@YouTubewwPDB FoundationwwPDB
RCSB PDBPDBeBMRBAdv. SearchSearch help

3LU9

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

Summary for 3LU9
Entry DOI10.2210/pdb3lu9/pdb
Related1SHH
DescriptorProthrombin, Proteinase-activated receptor 1, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
Functional Keywordsserine 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
Biological sourceHomo sapiens (human)
More
Total number of polymer chains6
Total formula weight76841.28
Authors
Gandhi, P.S.,Chen, Z.,Di Cera, E. (deposition date: 2010-02-17, release date: 2010-03-16, Last modification date: 2024-11-06)
Primary citationGandhi, 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
Cited by
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
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.8 Å)
Structure validation

227344

數據於2024-11-13公開中

PDB statisticsPDBj update infoContact PDBjnumon