title: Sequence analysis of steroid- and prostaglandin-metabolizing enzymes: application to understanding catalysis.
abstract: Amino acid sequence comparisons have revealed that mammalian 11 beta-hydroxysteroid and 17 beta-hydroxysteroid dehydrogenases and bacterial 3 alpha, 20 beta- and 3 beta-hydroxysteroid dehydrogenases are homologs; that is, these enzymes are descended from a common ancestor. These steroid dehydrogenases are also homologous to human 15-hydroxyprostaglandin dehydrogenase and to proteins found in Rhizobia, bacteria that form nitrogen-fixing nodules in the roots of legumes. We constructed a multiple sequence alignment of these proteins, which, when combined with the recently determined tertiary structure of Streptomyces hydrogenans 3 alpha, 20 beta-hydroxysteroid dehydrogenase and a homologous enzyme, rat dihydropteridine reductase, identifies segments and residues that are likely to be structurally important in the functioning of these enzymes especially regarding specificity for NADPH and NADH.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla 92093-0623.
authors.forename: M E
authors.initials: ME
authors.lastname: Baker
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites / Q000502:physiology; D005075:Biological Evolution; D002384:Catalysis; D006913:Hydroxysteroid Dehydrogenases / Q000737:chemistry*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010802:Phylogeny; D011453:Prostaglandins / Q000378:metabolism*; D016415:Sequence Alignment; D013256:Steroids / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D011453:Prostaglandins; D013256:Steroids; D009243:NAD; D009249:NADP; D006913:Hydroxysteroid Dehydrogenases