View source for 4bdv


==CRYSTAL STRUCTURE OF A TRUNCATED B-DOMAIN HUMAN FACTOR VIII==
<StructureSection load='4bdv' size='340' side='right'caption='[[4bdv]], [[Resolution|resolution]] 3.98&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4bdv]] 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=4BDV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BDV 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]] 3.98&#8491;</td></tr>
<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=CU1:COPPER+(I)+ION'>CU1</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4bdv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bdv OCA], [https://pdbe.org/4bdv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bdv RCSB], [https://www.ebi.ac.uk/pdbsum/4bdv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bdv ProSAT]</span></td></tr>
</table>
== Disease ==
[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> 
== Function ==
[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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== Publication Abstract from PubMed ==
Abstract Coagulation factor VIII is a glycosylated, non-covalent heterodimer consisting of a heavy chain (A1-A2-B domains) and a light chain (A3-C1-C2 domains). The association of the chains, and the stability and function of the dimer depend on the presence of metal ions. We applied X-ray fluorescence, X-ray crystallographic structure determination with anomalous signals at different wavelengths, and colorimetric measurements to evaluate the metal binding sites in a recombinant factor VIII molecule, turoctocog alfa. We identified a metal binding site in domain A3 dominated by Cu+ binding and a site in domain A1 dominated by Zn2+ binding.

Evaluation of the metal binding sites in a recombinant coagulation factor VIII identifies two sites with unique metal binding properties.,Svensson LA, Thim L, Olsen OH, Nicolaisen EM Biol Chem. 2013 Jun 1;394(6):761-5. doi: 10.1515/hsz-2012-0298. PMID:23435097<ref>PMID:23435097</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Factor VIII|Factor VIII]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Nicolaisen EM]]
[[Category: Olsen OH]]
[[Category: Svensson LA]]
[[Category: Thim L]]