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1j3s
From Proteopedia
| 1j3s, 20 NMR models () | |||||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Contents |
Solution Structure of Reduced Recombinant Human Cytochrome c
The effect of tyrosine nitration on the physicochemical properties and reactivity of human respiratory cytochrome c has been extensively analyzed. A set of mutants, each bearing only one tyrosine out of the five present in the wild-type molecule, has been constructed in order to study the effect of each tyrosine nitration on the properties of the whole protein. Replacement of tyrosines by phenylalanines does not promote significant changes in the properties of the cytochrome. Nitration of wild-type cytochrome c promotes a drastic decrease (ca. 350 mV) in the midpoint redox potential, probably induced by nitration of both tyrosines 48 and 67. Nitration also promotes a significant decrease in the intrinsic reactivity of all the wild-type and mutant proteins. Nitration of mutant cytochromes and, in particular, of the wild-type protein significantly decreases their reactivity with cytochrome c oxidase, thereby suggesting that this alteration is due to an accumulative effect of different nitrations. The reactivity of mutants bearing tyrosine 67 and, to a lesser extent, tyrosine 74 is more affected by nitration, indicating that the change in reactivity of nitrated wild-type cytochrome c is mainly due to nitration of these tyrosine residues. Moreover, nitration of wild-type cytochrome c induces a significant loss in its ability to activate caspases because of the additive effect of nitration of several tyrosine groups, as inferred from the behavior of monotyrosine mutants.
Effect of nitration on the physicochemical and kinetic features of wild-type and monotyrosine mutants of human respiratory cytochrome c., Rodriguez-Roldan V, Garcia-Heredia JM, Navarro JA, De la Rosa MA, Hervas M, Biochemistry. 2008 Nov 25;47(47):12371-9. PMID:018956889
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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.
About this Structure
1j3s is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA.
See Also
Reference
- Rodriguez-Roldan V, Garcia-Heredia JM, Navarro JA, De la Rosa MA, Hervas M. Effect of nitration on the physicochemical and kinetic features of wild-type and monotyrosine mutants of human respiratory cytochrome c. Biochemistry. 2008 Nov 25;47(47):12371-9. PMID:18956889 doi:10.1021/bi800910v
- ↑ 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
