2n3y

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'''Unreleased structure'''
 
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The entry 2n3y is ON HOLD until Dec 14 2017
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==NMR structure of the Y48pCMF variant of human cytochrome c in its reduced state==
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<StructureSection load='2n3y' size='340' side='right'caption='[[2n3y]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2n3y]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N3Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N3Y 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">Solution NMR, 20 models</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=1PA:4-(CARBOXYMETHYL)-L-PHENYLALANINE'>1PA</scene>, <scene name='pdbligand=MH0:MESOHEME'>MH0</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=2n3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n3y OCA], [https://pdbe.org/2n3y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n3y RCSB], [https://www.ebi.ac.uk/pdbsum/2n3y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n3y ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Regulation of mitochondrial activity allows cells to adapt to changing conditions and to control oxidative stress, and its dysfunction can lead to hypoxia-dependent pathologies such as ischemia and cancer. Although cytochrome c phosphorylation-in particular, at tyrosine 48-is a key modulator of mitochondrial signaling, its action and molecular basis remain unknown. Here we mimic phosphorylation of cytochrome c by replacing tyrosine 48 with p-carboxy-methyl-l-phenylalanine (pCMF). The NMR structure of the resulting mutant reveals significant conformational shifts and enhanced dynamics around pCMF that could explain changes observed in its functionality: The phosphomimetic mutation impairs cytochrome c diffusion between respiratory complexes, enhances hemeprotein peroxidase and reactive oxygen species scavenging activities, and hinders caspase-dependent apoptosis. Our findings provide a framework to further investigate the modulation of mitochondrial activity by phosphorylated cytochrome c and to develop novel therapeutic approaches based on its prosurvival effects.
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Authors: Moreno-Beltran, B., Del Conte, R., Diaz-Quintana, A., De la Rosa, M.A., Turano, P., Diaz-Moreno, I.
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Structural basis of mitochondrial dysfunction in response to cytochrome c phosphorylation at tyrosine 48.,Moreno-Beltran B, Guerra-Castellano A, Diaz-Quintana A, Del Conte R, Garcia-Maurino SM, Diaz-Moreno S, Gonzalez-Arzola K, Santos-Ocana C, Velazquez-Campoy A, De la Rosa MA, Turano P, Diaz-Moreno I Proc Natl Acad Sci U S A. 2017 Apr 11;114(15):E3041-E3050. doi:, 10.1073/pnas.1618008114. Epub 2017 Mar 27. PMID:28348229<ref>PMID:28348229</ref>
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Description: NMR structure of the Y48pCMF variant of human cytochrome c in its reduced state
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Diaz-Moreno, I]]
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<div class="pdbe-citations 2n3y" style="background-color:#fffaf0;"></div>
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[[Category: Diaz-Quintana, A]]
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== References ==
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[[Category: Del Conte, R]]
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<references/>
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[[Category: Moreno-Beltran, B]]
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__TOC__
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[[Category: Turano, P]]
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</StructureSection>
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[[Category: De La Rosa, M.A]]
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: De la Rosa MA]]
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[[Category: Del Conte R]]
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[[Category: Diaz-Moreno I]]
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[[Category: Diaz-Quintana A]]
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[[Category: Moreno-Beltran B]]
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[[Category: Turano P]]

Current revision

NMR structure of the Y48pCMF variant of human cytochrome c in its reduced state

PDB ID 2n3y

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