Ghosh D, Sawicki M, Pletnev V, Erman M, Ohno S, Nakajin S, Duax W L
Department of Structural Biology, Hauptman-Woodward Medical Research Institute, Buffalo, New York 14203, USA.
J Biol Chem. 2001 May 25;276(21):18457-63. doi: 10.1074/jbc.M100538200. Epub 2001 Mar 8.
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.
猪睾丸羰基还原酶（PTCR）属于短链脱氢酶/还原酶（SDR）超家族，催化甾体和前列腺素上酮的NADPH依赖性还原反应。该酶与NADPH依赖性人15-羟基前列腺素脱氢酶/羰基还原酶的序列同一性接近85%。该酶在2.3埃分辨率下的三级结构揭示了SDR超家族的典型折叠，其使用酪氨酸-赖氨酸-丝氨酸三联体作为催化残基，但既不呈现区分所有SDR的功能性同四聚体，也不呈现同二聚体。它是SDR超家族中第一个已知的单体结构。在同样以单体形式具有活性的PTCR中，紧邻催化酪氨酸之前的一段41个残基的插入片段形成了一个全螺旋亚结构域，该亚结构域与界面螺旋堆积在一起，消除了超家族中保守的四螺旋束界面。PTCR结构中一条额外的反平行链也阻断了另一个由链介导的界面。这些新颖的结构特征为该酶单分子内一个催化位点的搭建提供了基础。
