EC Number   |
General Information |
Reference  |
|---|
   1.8.4.2 | physiological function |
posttranslocational protein folding in the Gram-positive biofilm-forming actinobacterium Actinomyces oris is mediated by membrane-bound thiol-disulfide oxidoreductase, MdbA, which catalyzes oxidative folding of nascent polypeptides transported by the Sec translocon |
745224 |
| 1.8.4.2 | metabolism |
enzyme reacts with glutathionylated substrates in a GSH-dependent ping pong mechanism. The pKa of GrxS12 catalytic Cys29 is very low (3.9) and makes GrxS12 itself sensitive to oxidation by H2O2 and to direct glutathionylation by nitrosoglutathione. Glutathionylated-GrxS12 is temporarily inactive until it is deglutathionylated by GSH |
762613 |
| 1.8.4.2 | physiological function |
isoform GRX5 is not an efficient catalyst of protein deglutathionylation nor exhibits distinct substrate specificities |
763028 |
| 1.8.4.2 | physiological function |
isoform GRX6 is not an efficient catalyst of protein deglutathionylation nor exhibits distinct substrate specificities |
763028 |
| 1.8.4.2 | physiological function |
CGFS-type GRX is not reduced by GSH and has an atypically low redox potential (-323 mV at pH 7.9). GRX3 can be reduced in the light by photoreduced ferredoxin and ferredoxin-thioredoxin reductase |
763241 |
| 1.8.4.2 | malfunction |
the truncation mutation (E87X) clearly disrupts the CHCH domain by removing a large portion of the protein from helix 2 onward. The other two mutations, W59C and W66R, are found within the first helix of COA6, where the side chains of each tryptophan face the bulk solvent, suggesting that these residues may facilitate interactions with their client proteins. Overexpression of the wild-type and mutant alleles of COA6 in control and COA6 patient fibroblasts shows that the W66R variant fails to rescue CcO activity. In contrast, expression of the W59C mutant leads to a partial recovery of CcO activity and COX2 levels. It seems that in most cell types residual levels of the partially functional W59C allele are not sufficient to support CcO assembly and mitochondrial respiration because coa6DELTA cells expressing the W59C variant do not exhibit respiratory growth. The human patient with the W59C mutation exhibits a severe CcO deficiency in cardiac tissue |
764441 |
| 1.8.4.2 | more |
the solution structure of COA6 reveals a coiled-coil-helix-coiled-coil-helix domain typical of redox-active proteins found in the mitochondrial inter-membrane space. COA6 structure analysis by NMR spectroscopy, overview |
-, 764441 |
| 1.8.4.2 | more |
the solution structure of COA6 reveals a coiled-coil-helix-coiled-coil-helix domain typical of redox-active proteins found in the mitochondrial inter-membrane space. COA6 structure analysis by NMR spectroscopy, overview. The conserved tryptophans W59 and W66 are critical for COA6 stability and possibly for their interactions with client proteins |
764441 |
| 1.8.4.2 | physiological function |
in eukaryotes, cellular respiration is driven by mitochondrial cytochrome c oxidase (CcO), an enzyme complex that requires copper cofactors for its catalytic activity. Insertion of copper into its catalytically active subunits, including COX2, is a complex process that requires metallochaperones and redox proteins including SCO1, SCO2, and COA6. COA6 is structurally tuned to function as a thiol-disulfide oxidoreductase in copper delivery to mitochondrial cytochrome c oxidase. COA6 can reduce the copper-coordinating disulfides of its client proteins, SCO1 and COX2, allowing for copper binding. Determination of the interaction surfaces and reduction potentials of COA6 and its client proteins provides a mechanism of how metallochaperone and disulfide reductase activities are coordinated to deliver copper to CcO, overview. COA6 acts as a disulfide reductase of SCO and COX2 proteins |
-, 764441 |
| 1.8.4.2 | physiological function |
in eukaryotes, cellular respiration is driven by mitochondrial cytochrome c oxidase (CcO), an enzyme complex that requires copper cofactors for its catalytic activity. Insertion of copper into its catalytically active subunits, including COX2, is a complex process that requires metallochaperones and redox proteins including SCO1, SCO2, and COA6. COA6 is structurally tuned to function as a thiol-disulfide oxidoreductase in copper delivery to mitochondrial cytochrome c oxidase. COA6 can reduce the copper-coordinating disulfides of its client proteins, SCO1 and COX2, allowing for copper binding. Determination of the interaction surfaces and reduction potentials of COA6 and its client proteins provides a mechanism of how metallochaperone and disulfide reductase activities are coordinated to deliver copper to CcO, overview. COA6 function can be bypassed in a reducing environment. Coa6 has a redox as opposed to a metallochaperone function in Cu delivery to Cox2. COA6 acts as a disulfide reductase of SCO and COX2 proteins. COA6 can reduce the disulfides of SCO proteins, generating free sulfhydryl groups. COA6 can also reduce the cysteines of COX2 |
764441 |
