3LU9
Crystal structure of human thrombin mutant S195A in complex with the extracellular fragment of human PAR1
Summary for 3LU9
| Entry DOI | 10.2210/pdb3lu9/pdb |
| Related | 1SHH |
| Descriptor | Prothrombin, Proteinase-activated receptor 1, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total) |
| Functional Keywords | 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 |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 6 |
| Total formula weight | 76841.28 |
| 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 citation | 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 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: 20236938DOI: 10.1074/jbc.M110.115337 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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