2oyi: Difference between revisions
New page: left|200px<br /> <applet load="2oyi" size="450" color="white" frame="true" align="right" spinBox="true" caption="2oyi, resolution 2.70Å" /> '''Crystal Structure o... |
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[[Image:2oyi.gif|left|200px]]<br /> | [[Image:2oyi.gif|left|200px]]<br /><applet load="2oyi" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="2oyi, resolution 2.70Å" /> | caption="2oyi, resolution 2.70Å" /> | ||
'''Crystal Structure of Fragment D of gammaD298,301A Fibrinogen with the Peptide Ligand Gly-Pro-Arg-Pro-Amide'''<br /> | '''Crystal Structure of Fragment D of gammaD298,301A Fibrinogen with the Peptide Ligand Gly-Pro-Arg-Pro-Amide'''<br /> | ||
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==Overview== | ==Overview== | ||
To determine the significance of the gamma2 calcium-binding site in fibrin, polymerization, we synthesized the fibrinogen variant, gammaD298,301A. We, expected these two alanine substitutions to prevent calcium binding in the, gamma2 site. We examined the influence of calcium on the polymerization of, gammaD298,301A fibrinogen, evaluated its plasmin susceptibility, and, solved 2.7 and 2.4 A crystal structures of the variant with the peptide, ligands Gly-Pro-Arg-Pro-amide (GPRP) and Gly-His-Arg-Pro-amide (GHRP), respectively. We found that thrombin-catalyzed polymerization of, gammaD298,301A fibrinogen was modestly impaired, whereas, batroxobin-catalyzed polymerization was significantly impaired relative to, normal fibrinogen. Notably, the influence of calcium on polymerization was, the same for the variant and for normal fibrinogen. Fibrinogen, gammaD298,301A was more susceptible to plasmin proteolysis in the presence, of GPRP. This finding suggests structural changes in the near-by "a", polymerization site. Comparisons of the structures revealed minor, conformational changes in the gamma294-301 loop that are likely, responsible for the weakened "a" site. When considered altogether, the, data suggest that the gamma2 calcium-binding site does not significantly, modulate polymerization. We cannot, however, rule out the possibility that, the weakened "a" polymerization site masks an important role for the, gamma2 calcium-binding site in normal polymerization. Somewhat, unexpectedly, the structure data showed that GPRP bound to the "b" site, and induced the same local conformational changes as GHRP to this site., This structure shows that "A:b" interactions can occur and suggests that, these may participate in normal polymerization. | To determine the significance of the gamma2 calcium-binding site in fibrin, polymerization, we synthesized the fibrinogen variant, gammaD298,301A. We, expected these two alanine substitutions to prevent calcium binding in the, gamma2 site. We examined the influence of calcium on the polymerization of, gammaD298,301A fibrinogen, evaluated its plasmin susceptibility, and, solved 2.7 and 2.4 A crystal structures of the variant with the peptide, ligands Gly-Pro-Arg-Pro-amide (GPRP) and Gly-His-Arg-Pro-amide (GHRP), respectively. We found that thrombin-catalyzed polymerization of, gammaD298,301A fibrinogen was modestly impaired, whereas, batroxobin-catalyzed polymerization was significantly impaired relative to, normal fibrinogen. Notably, the influence of calcium on polymerization was, the same for the variant and for normal fibrinogen. Fibrinogen, gammaD298,301A was more susceptible to plasmin proteolysis in the presence, of GPRP. This finding suggests structural changes in the near-by "a", polymerization site. Comparisons of the structures revealed minor, conformational changes in the gamma294-301 loop that are likely, responsible for the weakened "a" site. When considered altogether, the, data suggest that the gamma2 calcium-binding site does not significantly, modulate polymerization. We cannot, however, rule out the possibility that, the weakened "a" polymerization site masks an important role for the, gamma2 calcium-binding site in normal polymerization. Somewhat, unexpectedly, the structure data showed that GPRP bound to the "b" site, and induced the same local conformational changes as GHRP to this site., This structure shows that "A:b" interactions can occur and suggests that, these may participate in normal polymerization. | ||
==About this Structure== | ==About this Structure== | ||
2OYI is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 2OYI is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OYI OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: variant fibrinogen]] | [[Category: variant fibrinogen]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:17:10 2008'' | ||
Revision as of 16:17, 23 January 2008
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Crystal Structure of Fragment D of gammaD298,301A Fibrinogen with the Peptide Ligand Gly-Pro-Arg-Pro-Amide
OverviewOverview
To determine the significance of the gamma2 calcium-binding site in fibrin, polymerization, we synthesized the fibrinogen variant, gammaD298,301A. We, expected these two alanine substitutions to prevent calcium binding in the, gamma2 site. We examined the influence of calcium on the polymerization of, gammaD298,301A fibrinogen, evaluated its plasmin susceptibility, and, solved 2.7 and 2.4 A crystal structures of the variant with the peptide, ligands Gly-Pro-Arg-Pro-amide (GPRP) and Gly-His-Arg-Pro-amide (GHRP), respectively. We found that thrombin-catalyzed polymerization of, gammaD298,301A fibrinogen was modestly impaired, whereas, batroxobin-catalyzed polymerization was significantly impaired relative to, normal fibrinogen. Notably, the influence of calcium on polymerization was, the same for the variant and for normal fibrinogen. Fibrinogen, gammaD298,301A was more susceptible to plasmin proteolysis in the presence, of GPRP. This finding suggests structural changes in the near-by "a", polymerization site. Comparisons of the structures revealed minor, conformational changes in the gamma294-301 loop that are likely, responsible for the weakened "a" site. When considered altogether, the, data suggest that the gamma2 calcium-binding site does not significantly, modulate polymerization. We cannot, however, rule out the possibility that, the weakened "a" polymerization site masks an important role for the, gamma2 calcium-binding site in normal polymerization. Somewhat, unexpectedly, the structure data showed that GPRP bound to the "b" site, and induced the same local conformational changes as GHRP to this site., This structure shows that "A:b" interactions can occur and suggests that, these may participate in normal polymerization.
About this StructureAbout this Structure
2OYI is a Protein complex structure of sequences from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Probing the gamma2 Calcium-Binding Site: Studies with gammaD298,301A Fibrinogen Reveal Changes in the gamma294-301 Loop that Alter the Integrity of the "a" Polymerization Site(,)., Kostelansky MS, Lounes KC, Ping LF, Dickerson SK, Gorkun OV, Lord ST, Biochemistry. 2007 May 1;46(17):5114-23. Epub 2007 Apr 6. PMID:17411074
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