Cusack S, Härtlein M, Leberman R
European Molecular Biology Laboratory, Grenoble, France.
Nucleic Acids Res. 1991 Jul 11;19(13):3489-98. doi: 10.1093/nar/19.13.3489.
Class 2 aminoacyl-tRNA synthetases, which include the enzymes for alanine, aspartic acid, asparagine, glycine, histidine, lysine, phenylalanine, proline, serine and threonine, are characterised by three distinct sequence motifs 1,2 and 3 (reference 1). The structural and evolutionary relatedness of these ten enzymes are examined using alignments of primary sequences from prokaryotic and eukaryotic sources and the known three dimensional structure of seryl-tRNA synthetase from E. coli. It is shown that motif 1 forms part of the dimer interface of seryl-tRNA synthetase and motifs 2 and 3 part of the putative active site. It is further shown that the seven alpha 2 dimeric synthetases can be subdivided into class 2a (proline, threonine, histidine and serine) and class 2b (aspartic acid, asparagine and lysine), each subclass sharing several important characteristic sequence motifs in addition to those characteristic of class 2 enzymes in general. The alpha 2 beta 2 tetrameric enzymes (for glycine and phenylalanine) show certain special features in common as well as some of the class 2b motifs. In the alanyl-tRNA synthetase only motif 3 and possibly motif 2 can be identified. The sequence alignments suggest that the catalytic domain of other class 2 synthetases should resemble the antiparallel domain found in seryl-tRNA synthetase. Predictions are made about the sequence location of certain important helices and beta-strands in this domain as well as suggestions concerning which residues are important in ATP and amino acid binding. Strong homologies are found in the N-terminal extensions of class 2b synthetases and in the C-terminal extensions of class 2a synthetases suggesting that these putative tRNA binding domains have been added at a later stage in evolution to the catalytic domain.
2类氨酰-tRNA合成酶包括丙氨酸、天冬氨酸、天冬酰胺、甘氨酸、组氨酸、赖氨酸、苯丙氨酸、脯氨酸、丝氨酸和苏氨酸的合成酶，其特征在于具有三个不同的序列基序1、2和3（参考文献1）。利用来自原核生物和真核生物的一级序列比对以及大肠杆菌丝氨酰-tRNA合成酶的已知三维结构，研究了这十种酶的结构和进化相关性。结果表明，基序1构成丝氨酰-tRNA合成酶二聚体界面的一部分，基序2和3构成假定活性位点的一部分。进一步表明，七种α2二聚体合成酶可细分为2a类（脯氨酸、苏氨酸、组氨酸和丝氨酸）和2b类（天冬氨酸、天冬酰胺和赖氨酸），每个亚类除了具有2类酶的一般特征序列基序外，还共享几个重要的特征序列基序。α2β2四聚体酶（甘氨酸和苯丙氨酸的合成酶）显示出某些共同的特殊特征以及一些2b类基序。在丙氨酰-tRNA合成酶中，只能鉴定出基序3，可能还有基序2。序列比对表明，其他2类合成酶的催化结构域应类似于丝氨酰-tRNA合成酶中发现的反平行结构域。对该结构域中某些重要螺旋和β链的序列位置进行了预测，并就哪些残基在ATP和氨基酸结合中起重要作用提出了建议。在2b类合成酶的N端延伸区和2a类合成酶的C端延伸区发现了很强的同源性，这表明这些假定的tRNA结合结构域是在进化后期添加到催化结构域中的。
