Document Detail


Stereocontrol of arachidonic acid oxygenation by vertebrate lipoxygenases: newly cloned zebrafish lipoxygenase 1 does not follow the Ala-versus-Gly concept.
MedLine Citation:
PMID:  21880725     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Animal lipoxygenases (LOXs) are classified according to their specificity of arachidonic acid oxygenation, and previous sequence alignments suggested that S-LOXs contain a conserved Ala at a critical position at the active site but R-LOXs 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 (hydro(pero)xyeicosatetraenoic acid), and extensive mutation around Gly-410 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 Ala-to-Gly 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 and 12/15-LOX from rabbits, men, rhesus monkeys, orangutans, and mice, only minor alterations in the reaction specificity were observed. For these enzymes, S-HETE (hydroxyeicosatetraenoic acid) isomers remained the major oxygenation products, whereas chiral R-HETEs contributed only 10-30% to the total product mixture. Taken together these data indicate that the Ala-versus-Gly concept may not always predict the reaction specificity of vertebrate LOX isoforms.
Authors:
Christian Jansen; Katharina Hofheinz; Robert Vogel; Jana Roffeis; Monika Anton; Pallu Reddanna; Hartmut Kuhn; Matthias Walther
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-08-31
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-24     Completed Date:  2011-12-15     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  37804-12     Citation Subset:  IM    
Affiliation:
Institute of Biochemistry, University Medicine Berlin-Charité, Monbijoustrasse 2, D-10117 Berlin, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arachidonic Acid / genetics,  metabolism*
Humans
Isoenzymes / genetics,  metabolism
Lipoxygenase / genetics,  metabolism*
Macaca mulatta
Mice
Pongo
Rabbits
Species Specificity
Zebrafish / genetics,  metabolism*
Zebrafish Proteins / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Isoenzymes; 0/Zebrafish Proteins; 506-32-1/Arachidonic Acid; EC 1.13.11.12/Lipoxygenase
Comments/Corrections

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