Abstract
Porcine testicular carbonyl reductase (PTCR) belongs to the short chain dehydrogenases/reductases (SDR) superfamily and catalyzes the NADPH-dependent reduction of ketones on steroids and prostaglandins. The enzyme shares nearly 85% sequence identity with the NADPH-dependent human 15-hydroxyprostaglandin dehydrogenase/carbonyl reductase. The tertiary structure of the enzyme at 2.3 A reveals a fold characteristic of the SDR superfamily that uses a Tyr-Lys-Ser triad as catalytic residues, but exhibits neither the functional homotetramer nor the homodimer that distinguish all SDRs. It is the first known monomeric structure in the SDR superfamily. In PTCR, which is also active as a monomer, a 41-residue insertion immediately before the catalytic Tyr describes an all-helix subdomain that packs against interfacial helices, eliminating the four-helix bundle interface conserved in the superfamily. An additional anti-parallel strand in the PTCR structure also blocks the other strand-mediated interface. These novel structural features provide the basis for the scaffolding of one catalytic site within a single molecule of the enzyme.
Highlights
Porcine testicular carbonyl reductase (PTCR) belongs to the short chain dehydrogenases/reductases (SDR) superfamily and catalyzes the NADPH-dependent reduction of ketones on steroids and prostaglandins
In PTCR, which is active as a monomer, a 41-residue insertion immediately before the catalytic Tyr describes an all-helix subdomain that packs against interfacial helices, eliminating the fourhelix bundle interface conserved in the superfamily
The high level of 20-hydroxysteroid dehydrogenase (20-HSD) activity in the enzyme is demonstrated by the reduction of 20-carbonyl groups of C21-steroids, such as conversion of 17␣-hydroxyprogesterone to 17␣,20-dihydroxy-4-pregnen-3-one, which is present in pig testes during the neonatal stage [4, 5]
Summary
Porcine testicular carbonyl reductase (PTCR) belongs to the short chain dehydrogenases/reductases (SDR) superfamily and catalyzes the NADPH-dependent reduction of ketones on steroids and prostaglandins. In PTCR, which is active as a monomer, a 41-residue insertion immediately before the catalytic Tyr describes an all-helix subdomain that packs against interfacial helices, eliminating the fourhelix bundle interface conserved in the superfamily. The short chain dehydrogenases/reductases (SDR) catalyze critical steps of activation and inactivation of steroids, vitamins, prostaglandins, and other bioactive molecules by oxidation and reduction of hydroxyl and carbonyl groups, respectively [1]. A member of the SDR superfamily, the multifunctional enzyme porcine testicular carbonyl reductase (PTCR)/3␣/, 20-hydroxysteroid dehydrogenase (20-HSD), catalyzes the NADPH-dependent reduction of ketones on androgens, progestins, and prostaglandins, as well as aldehydes. We present the first crystal structure of a monomeric SDR and explain how the functional determinants of oligomeric SDRs could be retained within a monomer of PTCR having the basic SDR fold
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
