In search for function of two human orphan SDR enzymes: hydroxysteroid dehydrogenase like 2 (HSDL2) and short-chain dehydrogenase/reductase-orphan (SDR-O).
The protein superfamily of short-chain dehydrogenases/reductases (SDRs) today comprises over 20,000 members found in pro- and eukaryotes. Despite low amino acid sequence identity (only 15-30%), they share several similar characteristics in conformational structures, the N-terminal cofactor (NAD(P)/NAD(P)H) binding region being the most conserved. The enzymes catalyze oxido-reductive reactions and have a broad spectrum of substrates. Not all recently identified SDRs have been analyzed in detail yet, and we therefore characterized two rudimentarily annotated human SDR candidates: an orphan SDR (SDR-O) and hydroxysteroid dehydrogenase like 2 (HSDL2). We analyzed the amino acid sequence for cofactor preference, performed subcellular localization studies, and a screening for substrates of the enzymes, including steroid hormones and retinoids. None of both tested proteins showed a significant conversion of steroid hormones. However, the peroxisomal localization of human HSDL2 may suggest an involvement in fatty acid metabolism. For SDR-O a weak conversion of retinal into retinol was detectable in the presence of the cofactor NADH.
Kowalik
Dorota
D
Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Experimental Genetics, Genome Analysis Center, Neuherberg, Germany.
Haller
Ferdinand
F
Adamski
Jerzy
J
Moeller
Gabriele
G
D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D017931:DNA Primers; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013347:Subcellular Fractions / Q000201:enzymology; D013379:Substrate Specificity
D017931:DNA Primers; D011994:Recombinant Proteins; D010088:Oxidoreductases; C545210:HSDL2 protein, human; D006913:Hydroxysteroid Dehydrogenases