McFadden P N, Clarke S
Proc Natl Acad Sci U S A. 1982 Apr;79(8):2460-4. doi: 10.1073/pnas.79.8.2460.
Reversibly methylated aspartyl residues in human erythrocyte membrane proteins are shown to be in the "unnatural" D configuration. This is demonstrated by treatment of proteolytically derived aspartic acid beta-[3H]methyl ester with L- and D-amino-acid oxidases and by the resolution of diastereomeric L-leucyl dipeptides containing either L- or D-aspartic acid beta-methyl ester by ion-exchange chromatography. Based on this observation, we propose a novel role for eukaryotic protein carboxyl methyltransferases (protein O-methyltransferase; S-adenosyl-L-methionine:protein O-methyltransferase, EC 2.1.1.24). We suggest that these widely distributed enzymes function to recognize aspartyl residues that have racemized spontaneously for a subsequent repair reaction. This repair function is postulated to couple ester hydrolysis with the restoration of the original L configuration of the aspartyl residue. It is possible that similar types of racemization repair processes may occur by reversible covalent modifications at other residues. Other possible functions for D-aspartic acid beta-methyl ester residues in proteins are considered.
人红细胞膜蛋白中可逆甲基化的天冬氨酰残基显示为“非天然”的D构型。这通过用L-和D-氨基酸氧化酶处理蛋白水解衍生的天冬氨酸β-[³H]甲酯以及通过离子交换色谱法拆分含有L-或D-天冬氨酸β-甲酯的非对映异构L-亮氨酰二肽来证明。基于这一观察结果，我们提出了真核蛋白羧基甲基转移酶（蛋白O-甲基转移酶；S-腺苷-L-甲硫氨酸：蛋白O-甲基转移酶，EC 2.1.1.24）的一种新作用。我们认为这些广泛分布的酶的功能是识别自发消旋的天冬氨酰残基，以便进行后续的修复反应。推测这种修复功能将酯水解与天冬氨酰残基原始L构型的恢复相耦合。蛋白质中其他残基通过可逆共价修饰可能发生类似类型的消旋修复过程。还考虑了蛋白质中D-天冬氨酸β-甲酯残基的其他可能功能。
