Eklund H, Horjales E, Jörnvall H, Brändén C I, Jeffery J
Biochemistry. 1985 Dec 31;24(27):8005-12. doi: 10.1021/bi00348a025.
The amino acid sequence of sheep liver sorbitol dehydrogenase has been fitted to the high-resolution model of the homologous horse liver alcohol dehydrogenase by computer graphics. This has allowed construction of a model of sorbitol dehydrogenase that provides explanations why sorbitol is not a substrate for alcohol dehydrogenase, why ethanol is not a substrate for sorbitol dehydrogenase, and what determines its specificity for polyols. An important feature of the model is that one of the ligands to the active site zinc atom is a glutamic acid residue instead of a cysteine residue, which is the corresponding ligand in the homologous alcohol dehydrogenases. This is one component of the structural change that can be related to the different substrate specificities, showing how altered enzymic activity might be brought about by structural changes of the kind that it is now possible to introduce by site-directed mutagenesis and recombinant DNA techniques.
通过计算机图形技术，已将绵羊肝脏山梨醇脱氢酶的氨基酸序列与同源的马肝脏乙醇脱氢酶的高分辨率模型进行拟合。这使得构建出山梨醇脱氢酶模型成为可能，该模型能够解释为何山梨醇不是乙醇脱氢酶的底物、为何乙醇不是山梨醇脱氢酶的底物，以及是什么决定了其对多元醇的特异性。该模型的一个重要特征是，活性位点锌原子的配体之一是谷氨酸残基，而非同源乙醇脱氢酶中相应的半胱氨酸残基。这是与不同底物特异性相关的结构变化的一个组成部分，展示了通过定点诱变和重组DNA技术现在有可能引入的那种结构变化如何导致酶活性的改变。
