Linked Life Data

15337745

Source:http://linkedlifedata.com/resource/pubmed/id/15337745

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
45
pubmed:dateCreated
2004-11-1
pubmed:abstractText
Saccharomyces cerevisiae expresses multiple phospholipid hydroperoxide glutathione peroxidase (PHGPx)-like proteins in the absence of a classical glutathione peroxidase (cGPx), providing a unique system for dissecting the roles of these enzymes in vivo. The Gpx3 (Orp1/PHGpx3) protein transduces the hydroperoxide signal to the transcription factor Yap1, a function that could account for most GPX-dependent phenotypes. To test this hypothesis and ascertain what functions of Gpx3 can be shared by cGPx-like enzymes, we constructed a novel cGPx-like yeast enzyme, cGpx3. We confirmed that the "gap" sequences conserved among cGPxs but absent from aligned PHGPx sequences are the principal cause of the structural and functional differences of these enzymes. Peroxidase activity against a cGPx substrate was high in the cGpx3 construct, which was multimeric and had a peroxidase catalytic mechanism distinct from Gpx3; but cGpx3 was defective for phospholipid hydroperoxidase and signaling activities. cGpx3 did not complement the sensitivity to lipid peroxidation of a gpxDelta mutant, and the resistance to lipid peroxidation conferred by Gpx3 was independent of Yap1, establishing a functional role for Gpx3 phospholipid hydroperoxidase activity. Using the comparison between cGpx3 and Gpx3 in conjunction with other constructs to probe lipid peroxidation as a toxicity mechanism, we also ascertained that lipid peroxidation-dependent processes are a principal cause of cellular cadmium toxicity. The results demonstrate that phospholipid hydroperoxidase and Yap1-mediated signaling activities of Gpx3 have independent functional roles, although both functions depend on the absence of cGPx-like subunit interaction sites, and the results resolve more clearly the potential drivers of the differential selective evolution of GPx-like enzymes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
46652-8
pubmed:dateRevised
2009-7-24
pubmed:meshHeading
pubmed-meshheading:15337745-Alternative Splicing, pubmed-meshheading:15337745-Amino Acid Sequence, pubmed-meshheading:15337745-Cadmium, pubmed-meshheading:15337745-Chromatography, Gel, pubmed-meshheading:15337745-Cloning, Molecular, pubmed-meshheading:15337745-Escherichia coli, pubmed-meshheading:15337745-Glutathione Peroxidase, pubmed-meshheading:15337745-Humans, pubmed-meshheading:15337745-Lac Operon, pubmed-meshheading:15337745-Lipid Metabolism, pubmed-meshheading:15337745-Lipid Peroxidation, pubmed-meshheading:15337745-Molecular Sequence Data, pubmed-meshheading:15337745-Oxidation-Reduction, pubmed-meshheading:15337745-Peroxidases, pubmed-meshheading:15337745-Phenotype, pubmed-meshheading:15337745-Phospholipids, pubmed-meshheading:15337745-Saccharomyces cerevisiae, pubmed-meshheading:15337745-Saccharomyces cerevisiae Proteins, pubmed-meshheading:15337745-Sensitivity and Specificity, pubmed-meshheading:15337745-Sequence Homology, Amino Acid, pubmed-meshheading:15337745-Signal Transduction, pubmed-meshheading:15337745-Substrate Specificity, pubmed-meshheading:15337745-Time Factors, pubmed-meshheading:15337745-Transcription Factors, pubmed-meshheading:15337745-Water
pubmed:year
2004
pubmed:articleTitle
Genetic dissection of the phospholipid hydroperoxidase activity of yeast gpx3 reveals its functional importance.
pubmed:affiliation
Institute of Genetics, School of Biology, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.