Linked Life Data

14972329

Source:http://linkedlifedata.com/resource/pubmed/id/14972329

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-2-19
pubmed:abstractText
The human Sco2 protein is a cytochrome c oxidase assembly protein that participates in mitochondrial copper pathway, acting downstream of Cox17 protein. In a previous work, we detected mutations in the human SCO2 gene in three unrelated infants with fatal cardioencephalomyopathy and COX deficiency. In this study, full-length processed recombinant wild-type and two mutated forms of hSco2p (w/t-rhSco2p, E140K-rhSco2p, and S225F-rhSco2p) were produced in bacteria as soluble recombinant peptides for the first time and evaluated for differences in their physical state and ability to bind copper. Our data indicate the following: (a) w/t-rhSco2p and S225F-rhSco2p were found to be in a monomeric form in contrast to E140K-rhSco2p that was in a major non-reducible dimer and a minor monomer form; (b) wild-type and mutated rhSco2p exhibited clear differences in their physical conformational state, as shown by circular dichroism and thermal denaturation analyses; (c) copper binding studies showed that E140K-rhSco2p bound markedly less copper while S225F-rhSco2p more than expected as compared to amount of the copper bound with w/t-rhSco2p. rhCox17p served as positive control experiment. These data indicate that S225F and E140K mutations found in the SCO2 gene derived from patients alter the physical conformational state of encoded hSco2p that may disturb the normal copper transport pathway in mitochondria. These findings are valuable for understanding the molecular basis of fatal cardioencephalomyopathy and COX deficiency and for designing appropriate pharmacological interventions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1096-7192
pubmed:author
pubmed:issnType
Print
pubmed:volume
81
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
225-36
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Human recombinant mutated forms of the mitochondrial COX assembly Sco2 protein differ from wild-type in physical state and copper binding capacity.
pubmed:affiliation
Laboratory of Pharmacology, Department of Pharmaceutical Sciences, Aristotle University of Thessaloniki, Thessaloniki 54124, Macedonia, Greece.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't