SEQUENCE-ANALYSIS OF STEROID-METABOLIZING AND PROSTAGLANDIN-METABOLIZING ENZYMES - APPLICATION TO UNDERSTANDING CATALYSIS

Amino acid sequence comparisons have revealed that mammalian 11beta-hydroxysteroid and 17beta-hydroxysteroid dehydrogenases and bacterial 3alpha,20beta- and 3beta-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 3alpha,20beta-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.