Mycothiol-dependent formaldehyde dehydrogenase, a prokaryotic medium-chain dehydrogenase/reductase, phylogenetically links different eukaryotic alcohol dehydrogenases - Primary structure, conformational modelling and functional correlations
Mycothiol-dependent formaldehyde dehydrogenase, a prokaryotic medium-chain dehydrogenase/reductase, phylogenetically links different eukaryotic alcohol dehydrogenases - Primary structure, conformational modelling and functional correlations
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DOI：
10.1111/j.1432-1033.1997.00282.x
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发表时间：
1997-09-01
期刊：
影响因子：
--
通讯作者：
Jornvall, H
中科院分区：
文献类型：
--
作者：
Norin, A;VanOphem, PW;Jornvall, H
核霉菌蛋白依赖性甲醛脱氢酶在结构上通过对360二氧化蛋白链的肽分析以及通过与含锌含锌醇脱氢酶的构象性能的分子建模和功能相关性来表征。该结构被认为是一种不同的中链脱氢酶/还原酶/还原酶（MDR），在所有类别的二聚体醇脱氢酶簇（包括人类形式）和几种四聚体还原酶/脱水酶之间的系统发育位置中间。分子建模和功能上重要的残基表明，与MDR酒精脱氢酶的总体上相关的霉菌蛋白依赖性甲醛脱氢酶的折叠，催化和结构性锌原子的存在，但否则与不同的活性位点关系相吻合，但与不同的底物特异性特异性特异性相吻合，以及与第四纪结构差异兼容的改变环结构。 III类酒精脱氢酶中谷胱甘肽结合的典型残基不存在，这与菌硫醇因子不与谷胱甘肽密切相似。分子结构与“恒定”酒精脱氢酶（类型III类）和“可变”酒精脱氢酶（I类和II类类型）不同，进一步支持了依赖Mycothiro的甲醛的独特结构脱氢酶。这种与其他MDR酶之间内部链长差异的边界以不同的组合重合，支持整个蛋白质家族中环路区域有限变化的概念。
Prokaryotic mycothiol-dependent formaldehyde dehydrogenase has been structurally characterized by peptide analysis of the 360-residue protein chain and by molecular modelling and functional correlation with the conformational properties of zinc-containing alcohol dehydrofenases. The structure is found to be a divergent medium-chain dehydrogenase/reductase (MDR), at a phylogenetic position intermediate between the cluster of dimeric alcohol dehydrogenases of all classes (including the human forms), and several tetrameric reductases/dehydrogenases. Molecular modelling and functionally important residues suggest a fold of the mycothiol-dependent formaldehyde dehydrogenase related overall to that of MDR alcohol dehydrogenases, with the presence of the catalytic and structural zinc atoms, but otherwise much altered active-site relationships compatible with the different substrate specificity, and an altered loop structure compatible with differences in the quaternary structure. Residues typical of glutathione binding in class-III alcohol dehydrogenase are not present, consistent with that the mycothiol factor is not closely similar to glutathione. The molecular architecture is different from that of the 'constant' alcohol dehydrogenases (of class-III type) and the 'variable' alcohol dehydrogenases (of class-I and class-II types), further supporting the unique structure of mycothiol-dependent formaldehyde dehydrogenase. Borders of internal chain-length differences between this and other MDR enzymes coincide in different combinations, supporting the concept of limited changes in loop regions within this whole family of proteins.