Sequence of the D-aspartyl/L-isoaspartyl protein methyltransferase from human erythrocytes. Common sequence motifs for protein, DNA, RNA, and small molecule S-adenosylmethionine-dependent methyltransferases.
Sequence of the D-aspartyl/L-isoaspartyl protein methyltransferase from human erythrocytes. Common sequence motifs for protein, DNA, RNA, and small molecule S-adenosylmethionine-dependent methyltransferases.
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发表时间：
1989-11
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通讯作者：
D. Ingrosso;A. Fowler;J. Bleibaum;S. Clarke
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作者：
D. Ingrosso;A. Fowler;J. Bleibaum;S. Clarke
一种分布广泛的蛋白质甲基转移酶催化一个甲基从S-腺苷-蛋氨酸转移到L-天冬氨酸和L-天冬酰胺残基的D-天冬氨酸基和/或L-异天冬氨酸基的游离羧基上。这种酶被认为在AGE损伤的蛋白质的修复或分解代谢中起作用。我们在这里展示了人类红细胞中这种酶的更基本的同工酶I的完整氨基酸序列。通过对重叠的胰酶、金黄色葡萄球菌V8蛋白酶、破碎型假单胞菌内切酶Asp-N、溴化氰和羟胺产生的片段进行Edman降解和质谱分析，确定了该序列。NH2末端通过乙酰化修饰，该蛋白质含有226个氨基酸，计算出其相对分子质量为24,575。这一值与十二烷基硫酸酯存在下的聚丙烯酰胺凝胶电泳法和非变性条件下的凝胶过滤层析法测定的纯化蛋白的相对分子质量一致。在第22和119位发现两个不同的氨基酸残基可能表明存在等位基因变异或两个或更多密切相关的结构基因。最后，将该序列与核糖核酸、脱氧核糖核酸和小分子甲基转移酶以及其他S-腺苷甲硫氨酸利用酶的序列进行比较，结果表明，这些蛋白质中的许多具有三个序列相似性区域的元素，并且可能在结构上或进化上相关。
A widely distributed protein methyltransferase catalyzes the transfer of a methyl group from S-adenosyl-methionine to the free carboxyl groups of D-aspartyl and/or L-isoaspartyl derivatives of L-aspartyl and L-asparaginyl residues. This enzyme has been postulated to function in the repair or the catabolism of age-damaged proteins. We present here the complete amino acid sequence of the more basic isozyme I of this enzyme from human erythrocytes. The sequence was determined by Edman degradation and mass spectral analysis of overlapping trypsin, Staphylococcus aureus V8 protease, Pseudomonas fragi endoproteinase Asp-N, cyanogen bromide, and hydroxylamine-generated fragments. The NH2-terminus is modified by acetylation and the protein contains 226 amino acids for a calculated molecular weight of 24,575. This value is in good agreement with the molecular weight determined for the purified protein by polyacrylamide gel electrophoresis in the presence of dodecyl sulfate and by gel filtration chromatography under nondenaturing conditions. The identification of 2 different amino acid residues at both positions 22 and 119 may indicate the presence of allelic variants or of two or more closely related structural genes. Finally, comparison of this sequence with those of methyltransferases for RNA, DNA, and small molecules, as well as other S-adenosylmethionine-utilizing enzymes, shows that many of these proteins share elements of three regions of sequence similarity and may be structurally or evolutionarily related.