Cloning of the cDNA for human 5-lipoxygenase
The enzyme 5-lipoxygenase (5-LO) catalyzes the first two reactions in the pathway leading to the formation of leukotrienes from arachidonic acid. Leukotrienes are potent arachidonic acid metabolites possessing biological activities that suggest a role in the pathophysiology of allergic and inflammatory disease. To obtain structural information about 5-LO for use in developing anti-flammatory chemotherapeutic agents, the enzyme was purified from human polymorphonuclear leukocytes and the amino acid sequences were determined for several cyanogen bromide-derived peptides. A cDNA clone encoding a 674-amino acid protein containing all of the derived peptide sequences was isolated from a dimethyl sulfoxide differentiated HL60 cell cDNA library. The mRNA encoding 5-LO was detected only in differentiated HL60 cells and not in the undifferentiated cell line, indicating that the expression of 5-LO in this cell line is transcriptionally regulated. In addition, the human protein displays some amino acid sequence homology with several lipases and significant homology with the partial sequences of soybean and reticulocyte lipoxygenases. Thus, 5-LO appears to be a member of a larger family of related enzymes.
- Research Organization:
- Merck Sharp and Dohme Research Labs., West Point, PA (USA)
- OSTI ID:
- 6143379
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 85:2
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
OXYGENASES
AMINO ACID SEQUENCE
RECOMBINANT DNA
DNA-CLONING
ARACHIDONIC ACID
BIOLOGICAL PATHWAYS
INFLAMMATION
LYMPHOKINES
MAN
MESSENGER-RNA
PURIFICATION
ANIMALS
CARBOXYLIC ACIDS
CLONING
DNA
DNA HYBRIDIZATION
ENZYMES
GROWTH FACTORS
HYBRIDIZATION
MAMMALS
MITOGENS
MOLECULAR STRUCTURE
MONOCARBOXYLIC ACIDS
NUCLEIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
OXIDOREDUCTASES
PATHOLOGICAL CHANGES
PRIMATES
PROTEINS
RNA
SYMPTOMS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques