Porcine carbonyl reductase - Structural basis for a functional monomer in short chain dehydrogenases/reductases

Porcine testicular carbonyl reductase (PTCR) belongs to the short chain deh ydrogenases/reductases (SDR) superfamily and catalyzes the NADPH-dependent reduction of ketones on steroids and prostaglandins. The enzyme shares near ly 85% sequence identity with the NADPH-dependent human 15-hydroxyprostagla ndin dehydrogenase/carbonyl reductase. The tertiary structure of the enzyme at 2.3 Angstrom reveals a fold characteristic of the SDR superfamily that uses a Tyr-Lys-Ser triad as catalytic residues, but exhibits neither the fu nctional homotetramer nor the homodimer that distinguish all SDRs. It is th e first known monomeric structure in the SDR superfamily. In PTCR, which is also active as a monomer, a 41-residue insertion immediately before the ca talytic Tyr describes an ah-helix subdomain that packs against interfacial helices, eliminating the four-helix bundle interface conserved in the super family, An additional anti-parallel strand in the PTCR structure also block s the other strand-mediated interface. These novel structural features prov ide the basis for the scaffolding of one catalytic site within a single mol ecule of the enzyme.