Porcine Carbonyl Reductase STRUCTURAL BASIS FOR A FUNCTIONAL MONOMER IN SHORT CHAIN DEH~)ROGENASES/REDUCTASES*

Porcine testicular carbonyl reductase (PTCR) belongs to and ketones on a large number of xenobiotics (2, 3). The high the short chain dehydrogenases/reductases (SDR) super- Ievel of 20p-HSD activity in the enzyme is demonstrated by the fatnjly and catalyzes the NADPH-dependent reduction of reduction of 20-carbonyl groups of C21~steroids, such as conver-ketones on steroids and prostaglandins. The enzyme shares sion of 17a-hydroxyprogesterone to 17a,20p-dihydroxy-4-preg-nearly 85,~{o sequence identity with the NADPH-dependent nen-3-0ne, which is present in pig testes during the neonatal human 15-hydroxyprostaglandin dehydrogenase/carbonyl stage (4, 5). Purified PTCR also shows vigorous 3a- and 3p-reductase. The tertiary structure of the enzyme at 2.3 A HSD activities with 5a-androstan-17p-ol-3-0ne (5a-dihydrotes-reveals a fold characteristic of the SDR superfamily that tosterone) as a substrate (6). uses a I~r-Lys-Ser triad as catalyiic residues, but exilibits neither the functional homotetralner nor the homodimer PTCR is highly homologous to NADP(H)-dependent human that distinguish all SDRe. It is the first known monomeric and rat CRs, except for its 13 additional amino acid residues at structure in the SDR superfamily. In FTCR, which is also the C terminus (2). The sequence identity of PTCR with th