校对与甲基供体功能的演变。大肠杆菌甲硫氨酰 - tRNA合成酶将甲硫氨酸环化生成S - 甲基高半胱氨酸硫内酯。

Proofreading and the evolution of a methyl donor function. Cyclization of methionine to S-methyl homocysteine thiolactone by Escherichia coli methionyl-tRNA synthetase.

作者信息

Jakubowski H

机构信息

Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103.

出版信息

J Biol Chem. 1993 Mar 25;268(9):6549-53.

PMID:8454625

Abstract

A cyclic sulfonium compound, S-methyl homocysteine thiolactone (SMHT), is formed from methionine during in vitro tRNA aminoacylation catalyzed by Escherichia coli methionyl-tRNA synthetase. The mechanism of SMHT formation involves enzymatic deacylation of Met-tRNA (k = 0.06 s-1) and, to a lesser extent, Met-AMP (k = 0.02 s-1). Cyclization of methionine, reminiscent of cyclization of homocysteine during editing, illustrates the limited ability of methionyl-tRNA synthetase to discriminate against the cognate methionine at the editing site designed for the noncognate homocysteine. In early stages of biotic evolution, SMHT, a sulfonium compound, may have fulfilled the present day methyl donor function of S-adenosylmethionine. Existing homologies between methionyl-tRNA synthetase and S-adenosylmethionine synthetase indicate evolutionary relatedness of the two proteins.

摘要

一种环状锍化合物，即S-甲基高半胱氨酸硫内酯（SMHT），在体外由大肠杆菌甲硫氨酰-tRNA合成酶催化的tRNA氨基酰化过程中由蛋氨酸形成。SMHT形成的机制涉及Met-tRNA的酶促脱酰基作用（k = 0.06 s-1），以及在较小程度上涉及Met-AMP的酶促脱酰基作用（k = 0.02 s-1）。蛋氨酸的环化，类似于编辑过程中高半胱氨酸的环化，说明了甲硫氨酰-tRNA合成酶在为非同源高半胱氨酸设计的编辑位点上区分同源蛋氨酸的能力有限。在生物进化的早期阶段，一种锍化合物SMHT可能已经履行了当今S-腺苷甲硫氨酸的甲基供体功能。甲硫氨酰-tRNA合成酶和S-腺苷甲硫氨酸合成酶之间现有的同源性表明这两种蛋白质在进化上具有相关性。