Workun Gregory J, Moquin Kamila, Rothery Richard A, Weiner Joel H
Membrane Protein Research Group, Department of Biochemistry, University of Alberta, 474 Medical Sciences Building, Edmonton, Alberta T6G 2H7, Canada.
Microbiol Mol Biol Rev. 2008 Jun;72(2):228-48, table of contents. doi: 10.1128/MMBR.00041-07.
The importance of molybdoenzymes is exemplified both by the debilitating and fatal human diseases caused by their deficiency and by their persistence throughout evolution. Here, we show that the protein fold of the molybdopyranopterin-containing domain of sulfite oxidase (the SUOX fold) can be found in all three domains of life. Analyses of sequence data and protein structure comparisons (secondary structure matching) show that the SUOX fold is found in enzymes that have quite distinct macromolecular architectures comprising one or more domains and sometimes subsidiary subunits. These are summarized as follows: (i) animal SUOXs that contain an N-terminal cytochrome b(5) domain and an SUOX fold fused to a C-terminal dimerization domain; (ii) plant SUOX that contains an SUOX fold fused to a C-terminal dimerization domain; (iii) the YedY protein from Escherichia coli, which comprises only the SUOX fold; (iv) the sulfite dehydrogenase from Starkeya novella that contains the SUOX fold, a dimerization domain, and an additional c-type cytochrome subunit; and (v) the plant-type nitrate reductases, exemplified by that of Pichia angusta, that contain an N-terminal SUOX fold, a dimerization domain, a cytochrome b(5) domain, and a C-terminal NADH binding flavin adenine dinucleotide-containing domain. We used the primary sequences of the proteins containing an SUOX fold to mine 559 sequences of related proteins. A phylogeny of a nonredundant subset of these sequences was generated, and the resultant clades were categorized by sequence motif analyses in the context of the available protein structures. Based on the motif analyses, cladistics, and domain conservations, we are able to postulate a plausible pathway of SUOX fold enzyme evolution.
钼酶的重要性体现在它们缺乏时会导致使人衰弱甚至致命的人类疾病，以及它们在整个进化过程中的持久性。在这里，我们表明，亚硫酸盐氧化酶中含钼蝶呤结构域的蛋白质折叠（SUOX折叠）在生命的所有三个域中都能找到。对序列数据的分析和蛋白质结构比较（二级结构匹配）表明，SUOX折叠存在于具有相当不同的大分子结构的酶中，这些结构包括一个或多个结构域，有时还有辅助亚基。这些总结如下：（i）动物亚硫酸盐氧化酶，其包含一个N端细胞色素b5结构域和一个与C端二聚化结构域融合的SUOX折叠；（ii）植物亚硫酸盐氧化酶，其包含一个与C端二聚化结构域融合的SUOX折叠；（iii）来自大肠杆菌的YedY蛋白，其仅包含SUOX折叠；（iv）来自新金色单胞菌的亚硫酸盐脱氢酶，其包含SUOX折叠、一个二聚化结构域和一个额外的c型细胞色素亚基；以及（v）植物型硝酸还原酶，以奥古斯塔毕赤酵母的硝酸还原酶为例，其包含一个N端SUOX折叠、一个二聚化结构域、一个细胞色素b5结构域和一个C端NADH结合含黄素腺嘌呤二核苷酸结构域。我们使用包含SUOX折叠的蛋白质的一级序列来挖掘559个相关蛋白质的序列。生成了这些序列的非冗余子集的系统发育树，并根据可用蛋白质结构的背景下的序列基序分析对所得的进化枝进行了分类。基于基序分析、分支分类和结构域保守性，我们能够推测出SUOX折叠酶进化的合理途径。
