3p6z
From Proteopedia
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.<ref>PMID:2856554</ref> | [https://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.<ref>PMID:2856554</ref> | ||
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| - | == Publication Abstract from PubMed == | ||
| - | Thrombin-catalyzed activation of coagulation factor V (FV) is an essential positive feedback reaction within the blood clotting system. Efficient processing at the amino- (Arg(709)-Ser(710)) and carboxy-terminal activation cleavage sites (Arg(1545)-Ser(1546)) requires initial substrate interactions with two clusters of positively charged residues on the proteinase surface, exosites I and II. We addressed the mechanism of activation of human FV using peptides that cover the entire acidic regions preceding these cleavage sites, FV(657-709) (FVa2) and FV(1481-1545) (FVa3). FVa2 appears to interact mostly with exosite I, while both exosites are involved in interactions with the carboxy-terminal linker. The 1.7-A crystal structure of irreversibly inhibited thrombin bound to FVa2 unambiguously reveals docking of FV residues Glu(666)-Glu(672) to exosite I. These findings were confirmed in a second, medium-resolution structure of FVa2 bound to the benzamidine-inhibited proteinase. Our results suggest that the acidic A2-B domain linker is involved in major interactions with thrombin during cofactor activation, with its more NH(2)-terminal hirudin-like sequence playing a critical role. Modeling experiments indicate that FVa2, and likely also FVa3, wrap around thrombin in productive thrombin*FV complexes that cover a large surface of the activator to engage the active site. | ||
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| - | Structural basis of thrombin-mediated factor V activation: the Glu666-Glu672 sequence is critical for processing at the heavy chain-B domain junction.,Corral-Rodriguez MA, Bock PE, Hernandez-Carvajal E, Gutierrez-Gallego R, Fuentes-Prior P Blood. 2011 May 9. PMID:21555742<ref>PMID:21555742</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
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| - | <div class="pdbe-citations 3p6z" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Revision as of 14:05, 13 March 2024
Structural basis of thrombin mediated factor V activation: essential role of the hirudin-like sequence Glu666-Glu672 for processing at the heavy chain-B domain junction
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