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2oyh

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Revision as of 07:06, 22 August 2018

Crystal Structure of Fragment D of gammaD298,301A Fibrinogen with the Peptide Ligand Gly-His-Arg-Pro-Amide

Structural highlights

2oyh is a 10 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	1lt9, 1ltj, 1re3, 1re4, 1rf0, 1rf1, 1jy2, 1fzg, 2ffd, 2oyi
Gene:	FGA (HUMAN), FGB (HUMAN), FGG (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[FIBA_HUMAN] Defects in FGA are a cause of congenital afibrinogenemia (CAFBN) [MIM: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: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.^[1] [FIBG_HUMAN] Defects in FGG are a cause of congenital afibrinogenemia (CAFBN) [MIM:202400]. This rare autosomal recessive disorder is characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. Note=Patients with congenital fibrinogen abnormalities can manifest different clinical pictures. Some cases are clinically silent, some show a tendency toward bleeding and some show a predisposition for thrombosis with or without bleeding. [FIBB_HUMAN] Defects in FGB are a cause of congenital afibrinogenemia (CAFBN) [MIM:202400]. This rare autosomal recessive disorder is characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. Note=Patients with congenital fibrinogen abnormalities can manifest different clinical pictures. Some cases are clinically silent, some show a tendency toward bleeding and some show a predisposition for thrombosis with or without bleeding.

Function

[FIBA_HUMAN] Fibrinogen has a double function: yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation. [FIBG_HUMAN] Fibrinogen has a double function: yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation. [FIBB_HUMAN] Fibrinogen has a double function: yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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.

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Benson MD, Liepnieks J, Uemichi T, Wheeler G, Correa R. Hereditary renal amyloidosis associated with a mutant fibrinogen alpha-chain. Nat Genet. 1993 Mar;3(3):252-5. PMID:8097946 doi:http://dx.doi.org/10.1038/ng0393-252
↑ Kostelansky MS, Lounes KC, Ping LF, Dickerson SK, Gorkun OV, Lord ST. 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. Biochemistry. 2007 May 1;46(17):5114-23. Epub 2007 Apr 6. PMID:17411074 doi:10.1021/bi602607a

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2oyh"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Fragment D of gammaD298,301A Fibrinogen with the Peptide Ligand Gly-His-Arg-Pro-Amide==
 <StructureSection load='2oyh' size='340' side='right' caption='[[2oyh]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1lt9|1lt9]], [[1ltj|1ltj]], [[1re3|1re3]], [[1re4|1re4]], [[1rf0|1rf0]], [[1rf1|1rf1]], [[1jy2|1jy2]], [[1fzg|1fzg]], [[2ffd|2ffd]], [[2oyi|2oyi]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FGA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), FGB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), FGG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2oyh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oyh OCA], [http://pdbe.org/2oyh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2oyh RCSB], [http://www.ebi.ac.uk/pdbsum/2oyh PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2oyh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oyh OCA], [http://pdbe.org/2oyh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2oyh RCSB], [http://www.ebi.ac.uk/pdbsum/2oyh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2oyh ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 16: / Line 17: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/oy/2oyh_consurf.spt"</scriptWhenChecked>
+    <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/initialview01.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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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;">

2oyh

From Proteopedia

Revision as of 07:06, 22 August 2018

Crystal Structure of Fragment D of gammaD298,301A Fibrinogen with the Peptide Ligand Gly-His-Arg-Pro-Amide

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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