A MOLECULAR-MODEL FOR CINNAMYL ALCOHOL-DEHYDROGENASE, A PLANT AROMATIC ALCOHOL-DEHYDROGENASE INVOLVED IN LIGNIFICATION
A MOLECULAR-MODEL FOR CINNAMYL ALCOHOL-DEHYDROGENASE, A PLANT AROMATIC ALCOHOL-DEHYDROGENASE INVOLVED IN LIGNIFICATION
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DOI：
10.1016/0167-4838(93)90063-w
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发表时间：
1993-09-03
期刊：
影响因子：
--
通讯作者：
GORRICHON, L
中科院分区：
文献类型：
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作者：
MCKIE, JH;JAOUHARI, R;GORRICHON, L
通过对其克隆基因的序列分析发现，植物芳香醇脱氢酶，即肉桂醇脱氢酶（来自桉树的CAD2）与一系列脱氢酶具有同源性，这些脱氢酶包括醇脱氢酶、L - 苏氨酸 - 3 - 脱氢酶、D - 木糖还原酶和山梨醇脱氢酶。以马肝醇脱氢酶的X射线晶体学坐标为模板构建了CAD2的同源模型，必要时还从类似酶的其他类似结构区域获取了额外的建模信息。由此产生的结构模型合理地解释了CAD2的锌结合特性，表明其具有罗斯曼折叠（GXGXXG基序），并解释了该酶的A类立体特异性（从底物醇上移除pro - R氢）和芳香底物特异性。基于同源模型设计了一系列潜在的配体，并测试了它们对CAD2和马肝醇脱氢酶的抑制作用。
The plant aromatic alcohol dehydrogenase, cinnamyl alcohol dehydrogenase (CAD2 from Eucalyptus) was found by sequence analysis of its cloned gene to be homologous to a range of dehydrogenases including alcohol dehydrogenases, L-threonine-3-dehydrogenase, D-xylose reductase and sorbitol dehydrogenase. A homology model of CAD2 was built using the X-ray crystallographic coordinates of horse-liver alcohol dehydrogenase to provide the template, with additional modelling input from other analogous regions of structure from similar enzymes where necessary. The structural model thus produced rationalised the Zn-binding properties of CAD2, indicated the possession of a Rossmann fold (GXGXXG motif), and explained the class A stereospecificity (pro-R hydrogen removal from substrate alcohol) and aromatic substrate specificity of the enzyme. A range of potential ligands was designed based on the homology model and tested as inhibitors of CAD2 and horse liver alcohol dehydrogenase.