Linked Life Data

19481615

Source:http://linkedlifedata.com/resource/pubmed/id/19481615

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2009-7-20
pubmed:abstractText
Lipoxygenases have been classified according to their specificity of fatty acid oxygenation and for several plant enzymes pH-dependent alterations in the product patterns have been reported. Assuming that the biological role of mammalian lipoxygenases is based on the formation of specific reaction products, pH-dependent alterations would impact enzymes' functionality. In this study we systematically investigated the pH-dependence of vertebrate lipoxygenases and observed a remarkable stability of the product pattern in the near physiological range for the wild-type enzyme species. Site-directed mutagenesis of selected amino acids and alterations in the substrate concentrations induced a more pronounced pH-dependence of the reaction specificity. For instance, for the V603H mutant of the human 15-lipoxygenase-2 8-lipoxygenation was dominant at acidic pH (65%) whereas 15-H(p)ETE was the major oxygenation product at pH 8. Similarly, the product pattern of the wild-type mouse 8-lipoxygenase was hardly altered in the near physiological pH range but H604F exchange induced strong pH-dependent alterations in the positional specificity. Taken together, our data suggest that the reaction specificities of wild-type vertebrate lipoxygenase isoforms are largely resistant towards pH alterations. However, we found that changes in the assay conditions (low substrate concentration) and introduction/removal of a critical histidine at the active site impact the pH-dependence of reaction specificity for some lipoxygenase isoforms.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:volume
1791
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
827-35
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Structural basis for pH-dependent alterations of reaction specificity of vertebrate lipoxygenase isoforms.
pubmed:affiliation
Institute of Biochemistry, University Medicine Berlin - Charité, Germany. matthias.walther@charite.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't