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==Crystal structure of A51V variant of Human Cytochrome c==
<StructureSection load='6duj' size='340' side='right'caption='[[6duj]], [[Resolution|resolution]] 1.82&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6duj]] 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=6DUJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DUJ 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]] 1.8220272&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEC:HEME+C'>HEC</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=6duj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6duj OCA], [https://pdbe.org/6duj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6duj RCSB], [https://www.ebi.ac.uk/pdbsum/6duj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6duj ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/CYC_HUMAN CYC_HUMAN] Defects in CYCS are the cause of thrombocytopenia type 4 (THC4) [MIM:[https://omim.org/entry/612004 612004]; also known as autosomal dominant thrombocytopenia type 4. Thrombocytopenia is the presence of relatively few platelets in blood. THC4 is a non-syndromic form of thrombocytopenia. Clinical manifestations of thrombocytopenia are absent or mild. THC4 may be caused by dysregulated platelet formation.<ref>PMID:18345000</ref> 
== Function ==
[https://www.uniprot.org/uniprot/CYC_HUMAN CYC_HUMAN] Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers this electron to the cytochrome oxidase complex, the final protein carrier in the mitochondrial electron-transport chain.  Plays a role in apoptosis. Suppression of the anti-apoptotic members or activation of the pro-apoptotic members of the Bcl-2 family leads to altered mitochondrial membrane permeability resulting in release of cytochrome c into the cytosol. Binding of cytochrome c to Apaf-1 triggers the activation of caspase-9, which then accelerates apoptosis by activating other caspases.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The A51V variant of human cytochrome c is linked to thrombocytopenia 4 (THC4), a condition that causes decreased blood platelet counts. A 1.82 A structure of the A51V variant shows only minor changes in tertiary structure relative to the wild-type (WT) protein. Guanidine hydrochloride denaturation demonstrates that the global stability of the A51V variant is 1.3 kcal/mol less than that of the WT protein. The midpoint pH, pH1/2, of the alkaline transition of the A51V variant is 1 unit less than that of the WT protein. Stopped-flow pH jump experiments show that the A51V substitution affects the triggering ionization for one of two kinetically distinguishable alkaline conformers and enhances the accessibility of a high-spin heme transient. The pH1/2 for acid unfolding of the A51V variant is 0.7 units higher than for that of the WT protein. Consistent with the greater accessibility of non-native conformers for the A51V variant, the kcat values for its peroxidase activity increase by 6- to 15-fold in the pH range of 5-8 versus those of the WT protein. These data along with previously reported data for the other THC4-linked variants, G41S and Y48H, underscore the role of Omega-loop C (residues 40-57) in modulating the peroxidase activity of cytochrome c early in apoptosis.

Naturally Occurring A51V Variant of Human Cytochrome c Destabilizes the Native State and Enhances Peroxidase Activity.,Lei H, Bowler BE J Phys Chem B. 2019 Oct 24;123(42):8939-8953. doi: 10.1021/acs.jpcb.9b05869. Epub, 2019 Oct 14. PMID:31557440<ref>PMID:31557440</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6duj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bowler BE]]
[[Category: Lei H]]