AMINOTRANSFERASES - DEMONSTRATION OF HOMOLOGY AND DIVISION INTO EVOLUTIONARY SUBGROUPS
AMINOTRANSFERASES - DEMONSTRATION OF HOMOLOGY AND DIVISION INTO EVOLUTIONARY SUBGROUPS
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DOI：
10.1111/j.1432-1033.1993.tb17953.x
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发表时间：
1993-06-01
期刊：
影响因子：
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通讯作者：
CHRISTEN, P
中科院分区：
文献类型：
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作者：
MEHTA, PK;HALE, TI;CHRISTEN, P
迄今为止，已知的维生素b6依赖酶的氨基酸序列共有150个，其中最大的氨基酸序列由转氨酶提供，有14种不同的酶的51个序列。通过序列比较、亲水模式和二级结构预测算法对所有转氨酶序列进行比对。根据转氨酶在结构上的亲缘关系，可将其分为4个亚群。第一类包括天冬氨酸、丙氨酸、酪氨酸、磷酸组氨酸和苯丙氨酸转氨酶；II亚群乙酰鸟氨酸、鸟氨酸、omega-氨基酸、4-氨基丁酸酯和二氨基精氨酸转氨酶；第三亚组d-丙氨酸和支链氨基酸转氨酶，第四亚组丝氨酸和磷酸丝氨酸转氨酶。（N-1）剖面分析，更严格的剖面分析应用[Gribskov， M., McLachlan, a . D.和Eisenberg， D. (1987) Proc. Natl Acad. Sci.]。USA 84, 4355-43581建立了各亚群酶之间的同源性，以及除亚群III外的所有亚群之间的同源性。然而，活性位点片段的相似性和不变残基周围的亲水模式表明，亚群III虽然是远亲，但也可能与其他转氨酶同源。在综合比对的基础上，提出了一种适用于转氨酶（AT）的新的氨基酸残基编号方法。在多对序列中，51个序列中约400个氨基酸残基中只有4个不变，即Gly(314AT)197、Asp/Glu(340AT)222、Lys(385AT)258和Arg(562AT)386，括号内未显示的数字与猪胞质天冬氨酸转氨酶的结构相对应。显然，转氨酶构成了一组同源蛋白质，这些蛋白质分化成亚群，除了一些例外，还分化成已经存在于普遍祖先细胞中的底物特异性个体酶。
A total of 150 amino acid sequences of vitamin B6-dependent enzymes are known to date, the largest contingent being furnished by the aminotransferases with 51 sequences of 14 different enzymes. All aminotransferase sequences were aligned by using algorithms for sequence comparison, hydropathy patterns and secondary structure predictions. The aminotransferases could be divided into four subgroups on the basis of their mutual structural relatedness. Subgroup I comprises aspartate, alanine, tyrosine, histidinol-phosphate, and phenylalanine aminotransferases; subgroup II acetylornithine, ornithine, omega-amino acid, 4-aminobutyrate and diaminopelargonate aminotransferases; subgroup III D-alanine and branched-chain amino acid aminotransferases, and subgroup IV serine and phosphoserine aminotransferases. (N-1) Profile analysis, a more stringent application of profile analysis [Gribskov, M., McLachlan, A. D. and Eisenberg, D. (1987) Proc. Natl Acad. Sci. USA 84, 4355-43581, established the homology among the enzymes of each subgroup as well as among all subgroups except subgroup III. However, similarity of active-site segments and the hydropathy patterns around invariant residues suggest that subgroup III, though most distantly related, might also be homologous with the other aminotransferases. On the basis of the comprehensive alignment, a new numbering of amino acid residues applicable to aminotransferases (AT) in general is proposed. In the multiply aligned sequences, only four out of a total of about 400 amino acid residues proved invariant in all 51 sequences, i.e. Gly(314AT)197, Asp/Glu(340AT)222, Lys(385AT)258 and Arg(562AT)386, the number not in parentheses corresponding to the structure of porcine cytosolic aspartate aminotransferase. Apparently, the aminotransferases constitute a group of homologous proteins which diverged into subgroups and, with some exceptions, into substrate-specific individual enzymes already in the universal ancestor cell.