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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions |
umls-concept:C0003691,
umls-concept:C0006556,
umls-concept:C0008633,
umls-concept:C0009015,
umls-concept:C0017262,
umls-concept:C0017428,
umls-concept:C0022192,
umls-concept:C0079866,
umls-concept:C0185117,
umls-concept:C0475264,
umls-concept:C0591833,
umls-concept:C0678594,
umls-concept:C1707271,
umls-concept:C2911684
|
| pubmed:issue |
19
|
| pubmed:dateCreated |
1994-6-22
|
| pubmed:databankReference | |
| pubmed:abstractText |
Two types of 12-lipoxygenase that catalyze the transformation of arachidonic acid to 12(S)-hydroperoxyeicosatetraenoic acid (12-HPETE) have been previously classified into platelet-type and leukocyte-type categories. Here, we document, for the first time, a molecular characterization of both forms within the same species. The amino acid sequence of the murine platelet 12-lipoxygenase deduced from its cDNA is 58% identical to the murine spleen/leukocyte 12-lipoxygenase. Expression constructs carrying the cDNAs for the two 12-lipoxygenase forms were introduced into human embryonic kidney 293 cells. The platelet-type enzyme metabolized arachidonic acid exclusively to 12-HPETE, whereas the leukocyte-type enzyme formed both 12-HPETE and 15-hydro(pero)xyeicosatetraenoic acid in a ratio of approximately 3:1. Linoleic acid was metabolized to a similar extent by the latter enzyme to 13-hydro(pero)xyoctadecadienoic acid but not by the platelet enzyme. Mutagenesis and deletion of the highly conserved lipoxygenase C-terminal isoleucine (Ile663), a residue believed to be involved in the non-heme iron atom coordination of all lipoxygenases, was performed. Deletion of Ile663 and substitution with most amino acids abolished enzyme activity. Only a valine substitution retained significant activity. These findings would tend to indicate a stringent requirement for the proper spatial alignment and folding of the C-terminal chain back into the core of the enzyme to interact with the iron atom by analogy with the recently determined crystal structure of a soybean lipoxygenase (Boyington, J. C., Gaffney, B. J., and Amzel, L. M. (1993) Science 260, 1482-1486). The platelet-type and leukocyte-type 12-lipoxygenase genes were cloned from a murine 129 Sv genomic library. Both genes are divided into a similar 14-exon/13-intron format, with the platelet-type gene being approximately twice the size of the leukocyte-type gene (13 versus 7.5 kilobases). A segment of a third gene was also isolated and probably represents a pseudogene derivative of either of these 12-lipoxygenase genes. All three genes were mapped to the central region of mouse chromosome 11 in a region of homology with human chromosome 17. Antibodies prepared against the two forms of 12-lipoxygenase revealed the differential distribution of the two enzymes throughout the mouse.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
May
|
| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
13
|
| pubmed:volume |
269
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
13979-87
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:8188678-Amino Acid Sequence,
pubmed-meshheading:8188678-Animals,
pubmed-meshheading:8188678-Arachidonate 12-Lipoxygenase,
pubmed-meshheading:8188678-Base Sequence,
pubmed-meshheading:8188678-Chromosome Mapping,
pubmed-meshheading:8188678-Cloning, Molecular,
pubmed-meshheading:8188678-DNA, Complementary,
pubmed-meshheading:8188678-Gene Expression,
pubmed-meshheading:8188678-Humans,
pubmed-meshheading:8188678-Isoleucine,
pubmed-meshheading:8188678-Leukocytes,
pubmed-meshheading:8188678-Mice,
pubmed-meshheading:8188678-Mice, Inbred C57BL,
pubmed-meshheading:8188678-Molecular Sequence Data,
pubmed-meshheading:8188678-Mutagenesis, Site-Directed,
pubmed-meshheading:8188678-Sequence Homology, Amino Acid,
pubmed-meshheading:8188678-Sequence Homology, Nucleic Acid,
pubmed-meshheading:8188678-Spleen
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| pubmed:year |
1994
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| pubmed:articleTitle |
cDNA cloning, expression, mutagenesis of C-terminal isoleucine, genomic structure, and chromosomal localizations of murine 12-lipoxygenases.
|
| pubmed:affiliation |
Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|