5o10

From Proteopedia

(Difference between revisions)

Revision as of 12:15, 26 August 2020

Y48H mutant of human cytochrome c

Structural highlights

5o10 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

Proteins performing multiple biochemical functions are called "moonlighting proteins" or extreme multifunctional (EMF) proteins. Mitochondrial cytochrome c is an EMF protein that binds multiple partner proteins to act as a signaling molecule, transfers electrons in the respiratory chain, and acts as a peroxidase in apoptosis. Mutations in the cytochrome c gene lead to the disease thrombocytopenia, which is accompanied by enhanced apoptotic activity. The Y48H variant arises from one such mutation and is found in the 40-57 Omega-loop, the lowest-unfolding free energy substructure of the cytochrome c fold. A 1.36 A resolution X-ray structure of the Y48H variant reveals minimal structural changes compared to the wild-type structure, with the axial Met80 ligand coordinated to the heme iron. Despite this, the intrinsic peroxidase activity is enhanced, implying that a pentacoordinate heme state is more prevalent in the Y48H variant, corroborated through determination of a Met80 "off rate" of >125 s(-1) compared to a rate of approximately 6 s(-1) for the wild-type protein. Heteronuclear nuclear magnetic resonance measurements with the oxidized Y48H variant reveal heightened dynamics in the 40-57 Omega-loop and the Met80-containing 71-85 Omega-loop relative to the wild-type protein, illustrating communication between these substructures. Placed into context with the G41S cytochrome c variant, also implicated in thrombocytopenia, a dynamic picture associated with this disease relative to cytochrome c is emerging whereby increasing dynamics in substructures of the cytochrome c fold serve to facilitate an increased population of the peroxidatic pentacoordinate heme state in the following order: wild type < G41S < Y48H.

Heightened Dynamics of the Oxidized Y48H Variant of Human Cytochrome c Increases Its Peroxidatic Activity.,Deacon OM, Karsisiotis AI, Moreno-Chicano T, Hough MA, Macdonald C, Blumenschein TMA, Wilson MT, Moore GR, Worrall JAR Biochemistry. 2017 Nov 21;56(46):6111-6124. doi: 10.1021/acs.biochem.7b00890., Epub 2017 Nov 8. PMID:29083920^[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
↑ Deacon OM, Karsisiotis AI, Moreno-Chicano T, Hough MA, Macdonald C, Blumenschein TMA, Wilson MT, Moore GR, Worrall JAR. Heightened Dynamics of the Oxidized Y48H Variant of Human Cytochrome c Increases Its Peroxidatic Activity. Biochemistry. 2017 Nov 21;56(46):6111-6124. doi: 10.1021/acs.biochem.7b00890., Epub 2017 Nov 8. PMID:29083920 doi:http://dx.doi.org/10.1021/acs.biochem.7b00890

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/5o10"

@@ Line 1: / Line 1: @@
 ==Y48H mutant of human cytochrome c==
-<StructureSection load='5o10' size='340' side='right' caption='[[5o10]], [[Resolution|resolution]] 1.36&Aring;' scene=''>
+<StructureSection load='5o10' size='340' side='right'caption='[[5o10]], [[Resolution|resolution]] 1.36&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5o10]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O10 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O10 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5o10]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O10 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5O10 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></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></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=5o10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o10 OCA], [http://pdbe.org/5o10 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o10 RCSB], [http://www.ebi.ac.uk/pdbsum/5o10 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o10 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=5o10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o10 OCA], [http://pdbe.org/5o10 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o10 RCSB], [http://www.ebi.ac.uk/pdbsum/5o10 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o10 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 20: @@
 </div>
 <div class="pdbe-citations 5o10" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Cytochrome C 3D structures|Cytochrome C 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Deacon, O M]]
 [[Category: Hough, M A]]

5o10

From Proteopedia

Revision as of 12:15, 26 August 2020

Y48H mutant 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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