Leukotriene B 12-hydroxydehydrogenase catalyzes the conversion of leukotriene B into its biologically less active metabolite, 12-oxo-leukotriene B. This is an initial and key step of metabolic inactivation of leukotriene B in various tissues other than leukocytes. Here we report the cDNA cloning for porcine and human enzymes from kidney cDNA libraries. A full-length cDNA of the porcine enzyme contains an open reading frame consisting of 987 base pairs, corresponding to 329 amino acids. The human enzyme showed a 97.1% homology with the porcine enzyme. Northern blotting of human tissues revealed its high expression in the kidney, liver, and intestine but not in leukocytes. The porcine enzyme was expressed as a glutathione S-transferase fusion protein in Escherichia coli, which exhibited similar characteristics with the native enzyme. Because the enzymes have a homology, in part, with NAD(P)-dependent alcohol dehydrogenases, a site-directed mutagenesis study was carried out. We found that three glycines at 152, 155, and 166 have crucial roles in the enzyme activity, possibly by producing an NADP binding pocket.

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