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5ty3

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Revision as of 12:23, 23 September 2020

Crystal structure of K72A variant of Human Cytochrome c

Structural highlights

5ty3 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CYC_HUMAN] Defects in CYCS are the cause of thrombocytopenia type 4 (THC4) [MIM: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.^[1]

Function

[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.

Publication Abstract from PubMed

We test the hypothesis that Lys72 suppresses the intrinsic peroxidase activity of human cytochrome c, as observed previously for yeast iso-1-cytochrome c [McClelland, L. J., et al. (2014) Proc. Natl. Acad. Sci. U. S. A. 111, 6648-6653]. A 1.25 A X-ray structure of K72A human cytochrome c shows that the mutation minimally affects structure. Guanidine hydrochloride denaturation demonstrates that the K72A mutation increases global stability by 0.5 kcal/mol. The K72A mutation also increases the apparent pKa of the alkaline transition, a measure of the stability of the heme crevice, by 0.5 unit. Consistent with the increase in the apparent pKa, the rate of formation of the dominant alkaline conformer decreases, and this conformer is no longer stabilized by proline isomerization. Peroxidase activity measurements show that the K72A mutation increases kcat by 1.6-4-fold at pH 7-10, an effect larger than that seen for the yeast protein. X-ray structures of wild type and K72A human cytochrome c indicate that direct interactions of Lys72 with the far side of Omega-loop D, which are seen in X-ray structures of horse and yeast cytochrome c and could suppress peroxidase activity, are lacking. Instead, we propose that the stronger effect of the K72A mutation on the peroxidase activity of human versus yeast cytochrome c results from relief of steric interactions between the side chains at positions 72 and 81 (Ile in human vs Ala in yeast), which suppress the dynamics of Omega-loop D necessary for the intrinsic peroxidase activity of cytochrome c.

Effect of a K72A Mutation on the Structure, Stability, Dynamics, and Peroxidase Activity of Human Cytochrome c.,Nold SM, Lei H, Mou TC, Bowler BE Biochemistry. 2017 Jul 5;56(26):3358-3368. doi: 10.1021/acs.biochem.7b00342. Epub, 2017 Jun 21. PMID:28598148^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Morison IM, Cramer Borde EM, Cheesman EJ, Cheong PL, Holyoake AJ, Fichelson S, Weeks RJ, Lo A, Davies SM, Wilbanks SM, Fagerlund RD, Ludgate MW, da Silva Tatley FM, Coker MS, Bockett NA, Hughes G, Pippig DA, Smith MP, Capron C, Ledgerwood EC. A mutation of human cytochrome c enhances the intrinsic apoptotic pathway but causes only thrombocytopenia. Nat Genet. 2008 Apr;40(4):387-9. Epub 2008 Mar 16. PMID:18345000 doi:ng.103
↑ Nold SM, Lei H, Mou TC, Bowler BE. Effect of a K72A Mutation on the Structure, Stability, Dynamics, and Peroxidase Activity of Human Cytochrome c. Biochemistry. 2017 Jul 5;56(26):3358-3368. doi: 10.1021/acs.biochem.7b00342. Epub, 2017 Jun 21. PMID:28598148 doi:http://dx.doi.org/10.1021/acs.biochem.7b00342

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5ty3"

@@ Line 1: / Line 1: @@
 ==Crystal structure of K72A variant of Human Cytochrome c==
-<StructureSection load='5ty3' size='340' side='right' caption='[[5ty3]], [[Resolution|resolution]] 1.25&Aring;' scene=''>
+<StructureSection load='5ty3' size='340' side='right'caption='[[5ty3]], [[Resolution|resolution]] 1.25&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5ty3]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TY3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TY3 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5ty3]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TY3 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5TY3 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEC:HEME+C'>HEC</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+</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>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ty3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ty3 OCA], [http://pdbe.org/5ty3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ty3 RCSB], [http://www.ebi.ac.uk/pdbsum/5ty3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ty3 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5ty3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ty3 OCA], [http://pdbe.org/5ty3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ty3 RCSB], [http://www.ebi.ac.uk/pdbsum/5ty3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ty3 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 20: @@
 </div>
 <div class="pdbe-citations 5ty3" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Cytochrome C 3D structures|Cytochrome C 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Bowler, B E]]
 [[Category: Lei, H]]

5ty3

From Proteopedia

Revision as of 12:23, 23 September 2020

Crystal structure of K72A variant of Human Cytochrome c

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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