Conversion of 10‐hydroxygeraniol to 10‐oxogeranial is a crucial step in iridoid biosynthesis. This reaction is catalyzed by a zinc‐dependent alcohol dehydrogenase, 10‐hydroxygeraniol dehydrogenase, belonging to the family of medium‐chain dehydrogenase/reductase (MDR). Here, we report the crystal structures of a novel 10‐hydroxygeraniol dehydrogenase from Catharanthus roseus in its apo and nicotinamide adenine dinucleotide phosphate (NADP⁺) bound forms. Structural analysis and docking studies reveal how subtle conformational differences of loops L1, L2, L3, and helix α9' at the orifice of the catalytic site confer differential activity of the enzyme toward various substrates, by modulating the binding pocket shape and volume. The present study, first of its kind, provides insights into the structural basis of substrate specificity of MDRs specific to linear substrates. Furthermore, comparison of apo and NADP⁺ bound structures suggests that the enzyme adopts open and closed states to facilitate cofactor binding.

中文翻译：

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10-羟基香叶醇脱氢酶的结构研究：一种来自长春花的新型线性底物特异性脱氢酶。


10-羟基香叶醇转化为10-氧香叶醛是环烯醚萜生物合成的关键步骤。该反应由锌依赖性醇脱氢酶、10-羟基香叶醇脱氢酶催化，属于中链脱氢酶/还原酶 (MDR) 家族。在这里，我们报道了一种来自长春花的新型 10-羟基香叶醇脱氢酶的apo和烟酰胺腺嘌呤二核苷酸磷酸 (NADP ⁺ ) 结合形式的晶体结构。结构分析和对接研究揭示了催化位点孔口处的环 L1、L2、L3 和螺旋 α9' 的细微构象差异如何通过调节结合袋形状和体积，赋予酶对各种底物的不同活性。本研究首次深入了解线性底物特异性 MDR 的底物特异性的结构基础。此外， apo和 NADP ⁺结合结构的比较表明该酶采用开放和闭合状态以促进辅因子结合。