Eye lens zeta-crystallin relationships to the family of "long-chain" alcohol/polyol dehydrogenases. Protein trimming and conservation of stable parts.
Eye lens zeta-crystallin relationships to the family of "long-chain" alcohol/polyol dehydrogenases. Protein trimming and conservation of stable parts.
复制标题
眼晶状体 zeta 晶状体蛋白与“长链”醇/多元醇脱氢酶家族的关系。
作者：
T. Borras;B. Persson;H. Jörnvall
豚鼠晶体zeta-Crystallin与含锌醇/多元醇脱氢酶家族有远亲关系。结合醇脱氢酶中催化锌原子的氨基酸残基在ζ -结晶蛋白中交换，这解释了已知酶活性的缺乏，而结合脱氢酶中非催化锌原子的氨基酸残基位于结晶蛋白中缺失的一段。因此，哺乳动物醇脱氢酶、多元醇脱氢酶和ζ -结晶蛋白构成了一系列表现出亚基金属含量连续变化的蛋白质，分别从两个锌原子变为一个锌原子，甚至可能为零锌原子。与四聚体脱氢酶一样，晶体蛋白缺乏二聚体脱氢酶中存在的环结构。值得注意的是，晶体蛋白是四聚体的，并且表明了额外亚基相互作用与环段缺失之间的相关性。晶体蛋白的缺失部分延伸，包含脱氢酶的第二个环。脱氢酶的辅酶结合结构域具有最大的保守性，其中心部分与晶体蛋白的结构域非常相似。甘氨酸是迄今为止最保守的残基，与醇脱氢酶构象中的弯曲位置相对应。折叠稳定部分的保存，环状结构的缺失，金属原子的缺失，以及晶体蛋白中只有一小部分氧化敏感半胱氨酸残基的存在（β 1脱氢酶亚基为5个，而β 1脱氢酶亚基为15个）表明晶态蛋白的稳定性增加，并且是醇脱氢酶家族的衍生物。这与晶晶体结晶蛋白功能所需的稳定酶结构的募集、通过这些脱氢酶或未知酶对蛋白质结构的修剪以及脱氢酶家族的多重变化是相容的。
zeta-Crystallin of guinea pig lens is distantly related to the family of zinc-containing alcohol/polyol dehydrogenases. The amino acid residues binding the catalytic zinc atom in the alcohol dehydrogenase are exchanged in zeta-crystallin, explaining lack of known enzyme activity, and those residues binding the noncatalytic zinc in the dehydrogenase are located in a segment absent from the crystallin. Mammalian alcohol dehydrogenase, polyol dehydrogenase, and zeta-crystallin therefore constitute a series of proteins exhibiting successive changes in subunit metal content, from two to one and probably zero zinc atoms, respectively. In common with tetrameric dehydrogenases, the crystallin lacks a loop structure present in the dimeric dehydrogenase. Significantly, the crystallin is tetrameric, and a correlation between extra subunit interactions and lack of the loop segment is indicated. The lacking segment in crystallin is extended, encompassing a second loop in the dehydrogenase. The greatest conservation corresponds to the coenzyme-binding domain of the dehydrogenases, the central parts of which are remarkably similar to those in the crystallin. Glycine is by far the most conserved residue and corresponds to positions at bends in the conformation of the alcohol dehydrogenase. The conservation of the stable parts of the fold, the absence of the loop structure, the lack of the metal atoms, and the presence of only a small proportion of oxidation-sensitive cysteine residues in crystallin (5 versus 15 in the beta 1 dehydrogenase subunit) suggest an increased stability of the lens protein and a derivation from the alcohol dehydrogenase family. This is compatible with the recruitment of stable enzyme structures for lens crystallin functions, with trimming of protein structures through these dehydrogenases or a yet unknown enzyme, and with multiple changes in the dehydrogenase family.