2pv9
From Proteopedia
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'''Crystal structure of murine thrombin in complex with the extracellular fragment of murine PAR4''' | '''Crystal structure of murine thrombin in complex with the extracellular fragment of murine PAR4''' | ||
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[[Category: Chen, Z.]] | [[Category: Chen, Z.]] | ||
[[Category: Mathews, F S.]] | [[Category: Mathews, F S.]] | ||
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| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 13:51:39 2008'' | |
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Revision as of 10:51, 4 May 2008
Crystal structure of murine thrombin in complex with the extracellular fragment of murine PAR4
Overview
It has been proposed that the cleaved form of protease-activated receptor 3 (PAR3) acts as a cofactor for thrombin cleavage and activation of PAR4 on murine platelets, but the molecular basis of this physiologically important effect remains elusive. X-ray crystal structures of murine thrombin bound to extracellular fragments of the murine receptors PAR3 ((38)SFNGGPQNTFEEFPLSDIE(56)) and PAR4 ((51)KSSDKPNPR downward arrow GYPGKFCANDSDTLELPASSQA(81), downward arrow = site of cleavage) have been solved at 2.0 and 3.5 A resolution, respectively. The cleaved form of PAR3, traced in the electron density maps from Gln-44 to Glu-56, makes extensive hydrophobic and electrostatic contacts with exosite I of thrombin through the fragment (47)FEEFPLSDIE(56). Occupancy of exosite I by PAR3 allosterically changes the conformation of the 60-loop and shifts the position of Trp-60d approximately 10 A with a resulting widening of the access to the active site. The PAR4 fragment, traced entirely in the electron density maps except for five C-terminal residues, clamps Trp-60d, Tyr-60a, and the aryl-binding site of thrombin with Pro-56 and Pro-58 at the P2 and P4 positions and engages the primary specificity pocket with Arg-59. The fragment then leaves the active site with Gly-60 and folds into a short helical turn that directs the backbone away from exosite I and over the autolysis loop. The structures demonstrate that thrombin activation of PAR4 may occur with exosite I available to bind cofactor molecules, like the cleaved form of PAR3, whose function is to promote substrate diffusion into the active site by allosterically changing the conformation of the 60-loop.
About this Structure
2PV9 is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.
Reference
Crystal structures of murine thrombin in complex with the extracellular fragments of murine protease-activated receptors PAR3 and PAR4., Bah A, Chen Z, Bush-Pelc LA, Mathews FS, Di Cera E, Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11603-8. Epub 2007 Jul 2. PMID:17606903 Page seeded by OCA on Sun May 4 13:51:39 2008
