3e1i: Difference between revisions

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-{{STRUCTURE_3e1i|  PDB=3e1i  |  SCENE=  }}
-===Crystal Structure of BbetaD432A Variant Fibrinogen Fragment D with the Peptide Ligand Gly-His-Arg-Pro-amide===
-{{ABSTRACT_PUBMED_19075185}}
-==Disease==
+==Crystal Structure of BbetaD432A Variant Fibrinogen Fragment D with the Peptide Ligand Gly-His-Arg-Pro-amide==
-[[http://www.uniprot.org/uniprot/FIBA_HUMAN FIBA_HUMAN]] Defects in FGA are a cause of congenital afibrinogenemia (CAFBN) [MIM:[http://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:[http://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>  [[http://www.uniprot.org/uniprot/FIBG_HUMAN FIBG_HUMAN]] Defects in FGG are a cause of congenital afibrinogenemia (CAFBN) [MIM:[http://omim.org/entry/202400 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. [[http://www.uniprot.org/uniprot/FIBB_HUMAN FIBB_HUMAN]] Defects in FGB are a cause of congenital afibrinogenemia (CAFBN) [MIM:[http://omim.org/entry/202400 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.
+<StructureSection load='3e1i' size='340' side='right'caption='[[3e1i]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3e1i]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E1I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E1I FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3e1i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e1i OCA], [https://pdbe.org/3e1i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e1i RCSB], [https://www.ebi.ac.uk/pdbsum/3e1i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e1i 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/e1/3e1i_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=3e1i ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Fibrinogen residue Bbeta432Asp is part of hole "b" that interacts with knob "B," whose sequence starts with Gly-His-Arg-Pro-amide (GHRP). Because previous studies showed BbetaD432A has normal polymerization, we hypothesized that Bbeta432Asp is not critical for knob "B" binding and that new knob-hole interactions would compensate for the loss of this Asp residue. To test this hypothesis, we solved the crystal structure of fragment D from BbetaD432A. Surprisingly, the structure (rfD-BbetaD432A+GH) showed the peptide GHRP was not bound to hole "b." We then re-evaluated the polymerization of this variant by examining clot turbidity, clot structure, and the rate of FXIIIa cross-linking. The turbidity and the rate of gamma-gamma dimer formation for BbetaD432A were indistinguishable compared with normal fibrinogen. Scanning electron microscopy showed no significant differences between the clots of BbetaD432A and normal, but the thrombin-derived clots had thicker fibers than clots obtained from batroxobin, suggesting that cleavage of FpB is more important than "B:b" interactions. We conclude that hole "b" and "B:b" knob-hole binding per se have no influence on fibrin polymerization.
-==Function==
+Fibrinogen variant BbetaD432A has normal polymerization but does not bind knob "B".,Bowley SR, Lord ST Blood. 2009 Apr 30;113(18):4425-30. Epub 2008 Dec 15. PMID:19075185<ref>PMID:19075185</ref>
-[[http://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. [[http://www.uniprot.org/uniprot/FIBG_HUMAN FIBG_HUMAN]] Fibrinogen has a double function: yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation. [[http://www.uniprot.org/uniprot/FIBB_HUMAN FIBB_HUMAN]] Fibrinogen has a double function: yielding monomers that polymerize into fibrin and acting as a cofactor in platelet aggregation.
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[3e1i]] is a 8 chain structure with sequence 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=3E1I OCA].
+</div>
+<div class="pdbe-citations 3e1i" style="background-color:#fffaf0;"></div>
 ==See Also==
 *[[Fibrinogen|Fibrinogen]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:019075185</ref><references group="xtra"/><references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Bowley, S R.]]
+[[Category: Large Structures]]
-[[Category: Lord, S T.]]
+[[Category: Synthetic construct]]
-[[Category: Blood clotting]]
+[[Category: Bowley SR]]
-[[Category: Blood coagulation]]
+[[Category: Lord ST]]
-[[Category: Disease mutation]]
-[[Category: Glycoprotein]]
-[[Category: Phosphoprotein]]
-[[Category: Pyrrolidone carboxylic acid]]
-[[Category: Secreted]]
-[[Category: Sulfation]]