1ny2: Difference between revisions
New page: left|200px<br /> <applet load="1ny2" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ny2, resolution 2.3Å" /> '''Human alpha thrombin... |
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'''Human alpha thrombin inhibited by RPPGF and hirugen'''<br /> | '''Human alpha thrombin inhibited by RPPGF and hirugen'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1NY2 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] Full crystallographic information is available from [http:// | 1NY2 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NY2 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: thrombosis ]] | [[Category: thrombosis ]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:31:21 2008'' | ||
Revision as of 17:31, 15 February 2008
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Human alpha thrombin inhibited by RPPGF and hirugen
OverviewOverview
Investigations determined the mechanism(s) by which Arg-Pro-Pro-Gly-Phe, (RPPGF) inhibits thrombin-induced platelet activation. High concentrations, of RPPGF inhibit thrombin-induced coagulant activity. RPPGF binds to the, active site of thrombin by forming a parallel beta-strand with, Ser214-Gly216 and interacts with His57, Asp189, and Ser195 of the, catalytic triad. RPPGF competitively inhibits alpha-thrombin from, hydrolyzing Sar-Pro-Arg-paranitroanilide with a Ki = 1.75 +/- 0.03 mM., Other mechanisms were sought to explain why RPPGF inhibits thrombin, activation of platelets at concentrations below that which inhibits its, active site. Soluble RPPGF blocks biotinylated NATLDPRSFLLR of the, thrombin cleavage site on protease-activated receptor (PAR)1 from binding, to the peptide RPPGC (IC50 = 20 microM). The soluble recombinant, extracellular domain of PAR1 (rPAR1EC) blocks biotinylated RPPGF binding, to rPAR1EC (IC50 = 50 microM) bound to microtiter plates, but rPAR1EC, deletion mutants missing the sequence LDPR or PRSF do not. RPPGF and, related forms prevent the thrombin-like enzyme thrombocytin from, proteolyzing rPAR1EC at concentrations that do not block thrombocytin's, active site. These studies indicate that RPPGF is a bifunctional inhibitor, of thrombin: it binds to PAR1 to prevent thrombin cleavage at Arg41 and, interacts with the active site of alpha-thrombin.
DiseaseDisease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this StructureAbout this Structure
1NY2 is a Protein complex structure of sequences from Homo sapiens. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.
ReferenceReference
Mechanisms of Arg-Pro-Pro-Gly-Phe inhibition of thrombin., Hasan AA, Warnock M, Nieman M, Srikanth S, Mahdi F, Krishnan R, Tulinsky A, Schmaier AH, Am J Physiol Heart Circ Physiol. 2003 Jul;285(1):H183-93. Epub 2003 Feb, 21. PMID:12598231
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