1de7
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(New page: 200px<br /> <applet load="1de7" size="450" color="white" frame="true" align="right" spinBox="true" caption="1de7, resolution 2.00Å" /> '''INTERACTION OF FACT...)
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Revision as of 14:24, 12 November 2007
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INTERACTION OF FACTOR XIII ACTIVATION PEPTIDE WITH ALPHA-THROMBIN: CRYSTAL STRUCTURE OF THE ENZYME-SUBSTRATE COMPLEX
Contents |
Overview
The serine protease thrombin proteolytically activates blood coagulation, factor XIII by cleavage at residue Arg(37); factor XIII in turn, cross-links fibrin molecules and gives mechanical stability to the blood, clot. The 2.0-A resolution x-ray crystal structure of human alpha-thrombin, bound to the factor XIII-(28-37) decapeptide has been determined. This, structure reveals the detailed atomic level interactions between the, factor XIII activation peptide and thrombin and provides the first high, resolution view of this functionally important part of the factor XIII, molecule. A comparison of this structure with the crystal structure of, fibrinopeptide A complexed with thrombin highlights several important, determinants of thrombin substrate interaction. First, the P1 and P2, residues must be compatible with the geometry and chemistry of the S1 and, S2 specificity sites in thrombin. Second, a glycine in the P5 position is, necessary for the conserved substrate conformation seen in both factor, XIII-(28-37) and fibrinopeptide A. Finally, the hydrophobic residues, which occupy the aryl binding site of thrombin determine the substrate, conformation further away from the catalytic residues. In the case of, factor XIII-(28-37), the aryl binding site is shared by hydrophobic, residues P4 (Val(34)) and P9 (Val(29)). A bulkier residue in either of, these sites may alter the substrate peptide conformation.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
1DE7 is a Protein complex structure of sequences from Homo sapiens with NA and CH2 as ligands. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.
Reference
Interaction of the factor XIII activation peptide with alpha -thrombin. Crystal structure of its enzyme-substrate analog complex., Sadasivan C, Yee VC, J Biol Chem. 2000 Nov 24;275(47):36942-8. PMID:10956659
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