2r7e

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{{STRUCTURE_2r7e| PDB=2r7e | SCENE= }}
 
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===Crystal Structure Analysis of Coagulation Factor VIII===
 
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{{ABSTRACT_PUBMED_17965321}}
 
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==Disease==
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==Crystal Structure Analysis of Coagulation Factor VIII==
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[[http://www.uniprot.org/uniprot/FA8_HUMAN FA8_HUMAN]] Defects in F8 are the cause of hemophilia A (HEMA) [MIM:[http://omim.org/entry/306700 306700]]. A disorder of blood coagulation characterized by a permanent tendency to hemorrhage. About 50% of patients have severe hemophilia resulting in frequent spontaneous bleeding into joints, muscles and internal organs. Less severe forms are characterized by bleeding after trauma or surgery. Note=Of particular interest for the understanding of the function of F8 is the category of CRM (cross-reacting material) positive patients (approximately 5%) that have considerable amount of F8 in their plasma (at least 30% of normal), but the protein is non-functional; i.e. the F8 activity is much less than the plasma protein level. CRM-reduced is another category of patients in which the F8C antigen and activity are reduced to approximately the same level. Most mutations are CRM negative, and probably affect the folding and stability of the protein.<ref>PMID:3012775</ref><ref>PMID:3122181</ref><ref>PMID:2833855</ref><ref>PMID:2835904</ref><ref>PMID:2499363</ref><ref>PMID:2506948</ref><ref>PMID:2510835</ref><ref>PMID:2495245</ref><ref>PMID:2498882</ref><ref>PMID:2104766</ref><ref>PMID:2105106</ref><ref>PMID:1973901</ref><ref>PMID:2105906</ref><ref>PMID:2106480</ref><ref>PMID:2107542</ref><ref>PMID:1908817</ref><ref>PMID:1908096</ref><ref>PMID:1851341</ref><ref>PMID:1356412</ref><ref>PMID:1639429</ref><ref>PMID:1349567</ref><ref>PMID:1301194</ref><ref>PMID:1301932</ref><ref>PMID:1301960</ref><ref>PMID:8449505</ref><ref>PMID:8322269</ref><ref>PMID:7579394</ref><ref>PMID:7794769</ref><ref>PMID:7759074</ref><ref>PMID:8644728</ref><ref>PMID:8639447</ref><ref>PMID:8759905</ref><ref>PMID:9029040</ref><ref>PMID:9326186</ref><ref>PMID:9341862</ref><ref>PMID:9886318</ref><ref>PMID:9450898</ref><ref>PMID:10215414</ref><ref>PMID:9603440</ref><ref>PMID:9452104</ref><ref>PMID:9792405</ref><ref>PMID:9829908</ref><ref>PMID:9569180</ref><ref>PMID:9569189</ref><ref>PMID:10554831</ref><ref>PMID:10338101</ref><ref>PMID:10408784</ref><ref>PMID:10404764</ref><ref>PMID:10910910</ref><ref>PMID:10910913</ref><ref>PMID:10691849</ref><ref>PMID:10886198</ref><ref>PMID:10800171</ref><ref>PMID:10896236</ref><ref>PMID:10612839</ref><ref>PMID:11410838</ref><ref>PMID:11298607</ref><ref>PMID:11442643</ref><ref>PMID:11442647</ref><ref>PMID:11554935</ref><ref>PMID:11748850</ref><ref>PMID:11341489</ref><ref>PMID:12351418</ref><ref>PMID:12406074</ref><ref>PMID:12199686</ref><ref>PMID:11857744</ref><ref>PMID:12203998</ref><ref>PMID:12325022</ref><ref>PMID:11858487</ref><ref>PMID:12195713</ref><ref>PMID:12930394</ref><ref>PMID:12871415</ref><ref>PMID:12614369</ref><ref>PMID:15682412</ref><ref>PMID:15810915</ref><ref>PMID:16805874</ref><ref>PMID:18184865</ref><ref>PMID:21371196</ref>
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<StructureSection load='2r7e' size='340' side='right'caption='[[2r7e]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2r7e]] is a 2 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=2R7E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R7E FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.7&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2r7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r7e OCA], [https://pdbe.org/2r7e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2r7e RCSB], [https://www.ebi.ac.uk/pdbsum/2r7e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2r7e ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/FA8_HUMAN FA8_HUMAN] Defects in F8 are the cause of hemophilia A (HEMA) [MIM:[https://omim.org/entry/306700 306700]. A disorder of blood coagulation characterized by a permanent tendency to hemorrhage. About 50% of patients have severe hemophilia resulting in frequent spontaneous bleeding into joints, muscles and internal organs. Less severe forms are characterized by bleeding after trauma or surgery. Note=Of particular interest for the understanding of the function of F8 is the category of CRM (cross-reacting material) positive patients (approximately 5%) that have considerable amount of F8 in their plasma (at least 30% of normal), but the protein is non-functional; i.e. the F8 activity is much less than the plasma protein level. CRM-reduced is another category of patients in which the F8C antigen and activity are reduced to approximately the same level. Most mutations are CRM negative, and probably affect the folding and stability of the protein.<ref>PMID:3012775</ref> <ref>PMID:3122181</ref> <ref>PMID:2833855</ref> <ref>PMID:2835904</ref> <ref>PMID:2499363</ref> <ref>PMID:2506948</ref> <ref>PMID:2510835</ref> <ref>PMID:2495245</ref> <ref>PMID:2498882</ref> <ref>PMID:2104766</ref> <ref>PMID:2105106</ref> <ref>PMID:1973901</ref> <ref>PMID:2105906</ref> <ref>PMID:2106480</ref> <ref>PMID:2107542</ref> <ref>PMID:1908817</ref> <ref>PMID:1908096</ref> <ref>PMID:1851341</ref> <ref>PMID:1356412</ref> <ref>PMID:1639429</ref> <ref>PMID:1349567</ref> <ref>PMID:1301194</ref> <ref>PMID:1301932</ref> <ref>PMID:1301960</ref> <ref>PMID:8449505</ref> <ref>PMID:8322269</ref> <ref>PMID:7579394</ref> <ref>PMID:7794769</ref> <ref>PMID:7759074</ref> <ref>PMID:8644728</ref> <ref>PMID:8639447</ref> <ref>PMID:8759905</ref> <ref>PMID:9029040</ref> <ref>PMID:9326186</ref> <ref>PMID:9341862</ref> <ref>PMID:9886318</ref> <ref>PMID:9450898</ref> <ref>PMID:10215414</ref> <ref>PMID:9603440</ref> <ref>PMID:9452104</ref> <ref>PMID:9792405</ref> <ref>PMID:9829908</ref> <ref>PMID:9569180</ref> <ref>PMID:9569189</ref> <ref>PMID:10554831</ref> <ref>PMID:10338101</ref> <ref>PMID:10408784</ref> <ref>PMID:10404764</ref> <ref>PMID:10910910</ref> <ref>PMID:10910913</ref> <ref>PMID:10691849</ref> <ref>PMID:10886198</ref> <ref>PMID:10800171</ref> <ref>PMID:10896236</ref> <ref>PMID:10612839</ref> <ref>PMID:11410838</ref> <ref>PMID:11298607</ref> <ref>PMID:11442643</ref> <ref>PMID:11442647</ref> <ref>PMID:11554935</ref> <ref>PMID:11748850</ref> <ref>PMID:11341489</ref> <ref>PMID:12351418</ref> <ref>PMID:12406074</ref> <ref>PMID:12199686</ref> <ref>PMID:11857744</ref> <ref>PMID:12203998</ref> <ref>PMID:12325022</ref> <ref>PMID:11858487</ref> <ref>PMID:12195713</ref> <ref>PMID:12930394</ref> <ref>PMID:12871415</ref> <ref>PMID:12614369</ref> <ref>PMID:15682412</ref> <ref>PMID:15810915</ref> <ref>PMID:16805874</ref> <ref>PMID:18184865</ref> <ref>PMID:21371196</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/FA8_HUMAN FA8_HUMAN] Factor VIII, along with calcium and phospholipid, acts as a cofactor for factor IXa when it converts factor X to the activated form, factor Xa.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r7/2r7e_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2r7e ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Factor VIII (fVIII) is a serum protein in the coagulation cascade that nucleates the assembly of a membrane-bound protease complex on the surface of activated platelets at the site of a vascular injury. Hemophilia A is caused by a variety of mutations in the factor VIII gene and typically requires replacement therapy with purified protein. We have determined the structure of a fully active, recombinant form of factor VIII (r-fVIII), which consists of a heterodimer of peptides, respectively containing the A1-A2 and A3-C1-C2 domains. The structure permits unambiguous modeling of the relative orientations of the 5 domains of r-fVIII. Comparison of the structures of fVIII, fV, and ceruloplasmin indicates that the location of bound metal ions and of glycosylation, both of which are critical for domain stabilization and association, overlap at some positions but have diverged at others.
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==Function==
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The tertiary structure and domain organization of coagulation factor VIII.,Shen BW, Spiegel PC, Chang CH, Huh JW, Lee JS, Kim J, Kim YH, Stoddard BL Blood. 2008 Feb 1;111(3):1240-7. Epub 2007 Oct 26. PMID:17965321<ref>PMID:17965321</ref>
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[[http://www.uniprot.org/uniprot/FA8_HUMAN FA8_HUMAN]] Factor VIII, along with calcium and phospholipid, acts as a cofactor for factor IXa when it converts factor X to the activated form, factor Xa.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[2r7e]] is a 2 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=2R7E OCA].
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</div>
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<div class="pdbe-citations 2r7e" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
*[[Factor VIII|Factor VIII]]
*[[Factor VIII|Factor VIII]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:017965321</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Shen, B W.]]
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[[Category: Large Structures]]
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[[Category: Stoddard, B L.]]
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[[Category: Shen BW]]
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[[Category: Acute phase]]
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[[Category: Stoddard BL]]
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[[Category: Blood clotting]]
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[[Category: Blood coagulation]]
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[[Category: C2 domain fold]]
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[[Category: Ceruloplasmin fold]]
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[[Category: Cupper protein fold]]
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[[Category: Disease mutation]]
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[[Category: Glycoprotein]]
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[[Category: Hemophilia]]
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[[Category: Metal-binding]]
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[[Category: Secreted]]
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[[Category: Sulfation]]
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Current revision

Crystal Structure Analysis of Coagulation Factor VIII

PDB ID 2r7e

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