2oyh: Difference between revisions

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-{{Seed}}
-[[Image:2oyh.png|left|200px]]
-<!--
+==Crystal Structure of Fragment D of gammaD298,301A Fibrinogen with the Peptide Ligand Gly-His-Arg-Pro-Amide==
-The line below this paragraph, containing "STRUCTURE_2oyh", creates the "Structure Box" on the page.
+<StructureSection load='2oyh' size='340' side='right'caption='[[2oyh]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2oyh]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OYH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OYH FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-{{STRUCTURE_2oyh|  PDB=2oyh  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2oyh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oyh OCA], [https://pdbe.org/2oyh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2oyh RCSB], [https://www.ebi.ac.uk/pdbsum/2oyh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2oyh ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/FIBA_HUMAN FIBA_HUMAN] Defects in FGA are a cause of congenital afibrinogenemia (CAFBN) [MIM:[https://omim.org/entry/202400 202400]. This is a rare autosomal recessive disorder characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. Note=The majority of cases of afibrinogenemia are due to truncating mutations. Variations in position Arg-35 (the site of cleavage of fibrinopeptide a by thrombin) leads to alpha-dysfibrinogenemias.  Defects in FGA are a cause of amyloidosis type 8 (AMYL8) [MIM:[https://omim.org/entry/105200 105200]; also known as systemic non-neuropathic amyloidosis or Ostertag-type amyloidosis. AMYL8 is a hereditary generalized amyloidosis due to deposition of apolipoprotein A1, fibrinogen and lysozyme amyloids. Viscera are particularly affected. There is no involvement of the nervous system. Clinical features include renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash.<ref>PMID:8097946</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/FIBA_HUMAN FIBA_HUMAN] Fibrinogen has a double function: yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/oy/2oyh_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2oyh ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+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.
-===Crystal Structure of Fragment D of gammaD298,301A Fibrinogen with the Peptide Ligand Gly-His-Arg-Pro-Amide===
+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<ref>PMID:17411074</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2oyh" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_17411074}}, adds the Publication Abstract to the page
+*[[Fibrinogen|Fibrinogen]]
-(as it appears on PubMed at http://www.pubmed.gov), where 17411074 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_17411074}}
+__TOC__
+</StructureSection>
-==Disease==
-Known disease associated with this structure: Afibrinogenemia, congenital OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134820 134820]], Amyloidosis, hereditary renal OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134820 134820]], Dysfibrinogenemia, alpha type, causing bleeding diathesis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134820 134820]], Dysfibrinogenemia, alpha type, causing recurrent thrombosis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134820 134820]], Afibrinogenemia, congenital OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134830 134830]], Dysfibrinogenemia, beta type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134830 134830]], Thrombophilia, dysfibrinogenemic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134830 134830]], Dysfibrinogenemia, gamma type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134850 134850]], Hypofibrinogenemia, gamma type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134850 134850]], Thrombophilia, dysfibrinogenemic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134850 134850]]
-==About this Structure==
-OYH is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OYH OCA].
-==Reference==
-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:[http://www.ncbi.nlm.nih.gov/pubmed/17411074 17411074]
 [[Category: Homo sapiens]]
-[[Category: Protein complex]]
+[[Category: Large Structures]]
-[[Category: Gorkun, O V.]]
+[[Category: Gorkun OV]]
-[[Category: Kostelansky, M S.]]
+[[Category: Kostelansky MS]]
-[[Category: Lord, S T.]]
+[[Category: Lord ST]]
-[[Category: Blood clotting]]
-[[Category: Fibrinogen]]
-[[Category: Fibrinogen fragment d]]
-[[Category: Gammad298,301a fibrinogen]]
-[[Category: Variant fibrinogen]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 01:07:43 2008''