Jörnvall H, von Bahr-Lindström H, Jeffery J
Eur J Biochem. 1984 Apr 2;140(1):17-23. doi: 10.1111/j.1432-1033.1984.tb08061.x.
Structural comparisons of sorbitol dehydrogenase with zinc-containing 'long' alcohol dehydrogenases reveal distant but clear relationships. An alignment suggests 93 positional identities with horse liver alcohol dehydrogenase (25% of 374 positions) and 73 identities with yeast alcohol dehydrogenase (20%). Sorbitol dehydrogenase forms a link between these distantly related alcohol dehydrogenases and is in some regions more similar to one of them that they are to each other. 43 residues (11%) are common to all three enzymes and include a heavy over-representation of glycine (half of all glycine residues in sorbitol dehydrogenase), showing the importance of space restrictions in protein structures. Four regions are well conserved, two in each domain of horse liver alcohol dehydrogenase. They are two segments close to the active-site zinc atom of the catalytic domain, and two in the central beta-pleated sheet strands of the coenzyme-binding domain. These similarities demonstrate the general importance of internal and central building units in proteins. Large variations affect a region adjacent to the third protein ligand to the active-site zinc atom in horse liver alcohol dehydrogenase. Such changes at active sites of related enzymes are unusual. Other large differences concern the segment around the non-catalytic zinc atom of horse liver alcohol dehydrogenase; three of its four cysteine ligands are absent from sorbitol dehydrogenase. Three segments with several exchanges correspond to a continuous region with superficial areas, inter-domain contacts and inter-subunit interactions in the catalytic domain of alcohol dehydrogenase. They may correlate with the altered quaternary structure of sorbitol dehydrogenase. Regions corresponding to top and bottom beta-strands in the coenzyme-binding domain of the alcohol dehydrogenase are also little conserved. Within sorbitol dehydrogenase, a large segment shows an internal similarity. The two distantly related alcohol dehydrogenases and sorbitol dehydrogenase form a triplet of enzymes illustrating basic protein relationships. They are ancestrally close enough to establish similarities, yet sufficiently divergent to illustrate changes in all but fundamental properties.
山梨醇脱氢酶与含锌“长链”醇脱氢酶的结构比较揭示了它们之间虽远但清晰的关系。序列比对显示，山梨醇脱氢酶与马肝醇脱氢酶有93个位置相同（占374个位置的25%），与酵母醇脱氢酶有73个位置相同（占20%）。山梨醇脱氢酶在这些远缘相关的醇脱氢酶之间建立了联系，并且在某些区域与其中一种的相似性比它们彼此之间的相似性更高。三种酶共有43个残基（占11%），其中甘氨酸的比例过高（山梨醇脱氢酶中所有甘氨酸残基的一半），这表明空间限制在蛋白质结构中的重要性。有四个区域高度保守，在马肝醇脱氢酶的每个结构域中各有两个。它们是靠近催化结构域活性位点锌原子的两个片段，以及辅酶结合结构域中央β折叠链中的两个片段。这些相似性表明了蛋白质内部和中央构建单元的普遍重要性。较大的变异影响了马肝醇脱氢酶中与活性位点锌原子的第三个蛋白质配体相邻的区域。相关酶活性位点的这种变化并不常见。其他较大差异涉及马肝醇脱氢酶非催化锌原子周围的片段；山梨醇脱氢酶中没有其四个半胱氨酸配体中的三个。有几个交换的三个片段对应于醇脱氢酶催化结构域中具有表面区域、结构域间接触和亚基间相互作用的连续区域。它们可能与山梨醇脱氢酶四级结构的改变有关。醇脱氢酶辅酶结合结构域中对应于顶部和底部β链的区域也不太保守。在山梨醇脱氢酶内部，一个大的片段显示出内部相似性。这两种远缘相关的醇脱氢酶和山梨醇脱氢酶形成了一组酶，说明了基本的蛋白质关系。它们在进化上足够接近以建立相似性，但又足够不同以说明除基本特性外的所有变化。
