PUBLICATION
Stereocontrol of arachidonic acid oxygenation by vertebrate lipoxygenases, newly cloned zebrafish lipoxygenase1 does not follow the A-vs-G concept
- Authors
- Jansen, C., Hofheinz, K., Vogel, R., Anton, M., Reddanna, P., Kuhn, H., and Walther, M.
- ID
- ZDB-PUB-110907-9
- Date
- 2011
- Source
- The Journal of biological chemistry 286(43): 37804-12 (Journal)
- Registered Authors
- Keywords
- eicosanoid, enzyme catalysis, leukotriene, lipid oxidation, lipoxygenase pathway, zebrafish, enantioselectivity, stereochemistry
- MeSH Terms
-
- Mice
- Macaca mulatta
- Rabbits
- Isoenzymes/genetics
- Isoenzymes/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Humans
- Animals
- Pongo
- Species Specificity
- Arachidonic Acid/genetics
- Arachidonic Acid/metabolism*
- Zebrafish/genetics
- Zebrafish/metabolism*
- Lipoxygenase/genetics
- Lipoxygenase/metabolism*
- PubMed
- 21880725 Full text @ J. Biol. Chem.
Citation
Jansen, C., Hofheinz, K., Vogel, R., Anton, M., Reddanna, P., Kuhn, H., and Walther, M. (2011) Stereocontrol of arachidonic acid oxygenation by vertebrate lipoxygenases, newly cloned zebrafish lipoxygenase1 does not follow the A-vs-G concept. The Journal of biological chemistry. 286(43):37804-12.
Abstract
Animal lipoxygenases (LOX) are classified according to their specificity of arachidonic acid oxygenation and previous sequence alignments suggested that S-LOX contain a conserved Ala at a critical position at the active site but R-LOX carry a Gly instead. Here we cloned, expressed and characterized a novel LOX-isoform from the model vertebrate Danio rerio (zebrafish) that carries a Gly at this critical position classifying this enzyme as putative arachidonic acid R-LOX. Surprisingly, the almost exclusive arachidonic acid oxygenation product was 12S-H(p)ETE and extensive mutation around G410 failed to induce R-lipoxygenation. This finding prompted us to explore the importance of the corresponding amino acids in other vertebrate S-LOXs. We found that A-to-G exchange in human 15-LOX2 and human platelet 12-LOX induced major alterations in the reaction specificity with an increase of specific R-oxygenation products. For mouse 5-LOX, for 12/15-LOX from rabbits, men, rhesus monkeys, orang-utans and mice only minor alterations in the reaction specificity were observed. For these enzymes S-HETE isomers remained the major oxygenation products whereas chiral R-HETEs contributed only 10-30% to the total product mixture. Taken together this data indicates that the A-vs-G concept may not always predict the reaction specificity of vertebrate LOX-isoforms.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping