硫尿苷合成酶的存在,甲基转移酶和假尿苷合酶(THUMP)结构域最初是通过生物信息学研究预测的。自从二十多年前对THUMP域的预测以来,已经鉴定了许多含有THUMP结构域的tRNA修饰酶。根据它们的酶活性,THUMP相关的tRNA修饰酶可分为五种类型,即4-硫尿苷合成酶,脱氨酶,甲基转移酶,乙酰转移酶和假尿苷合成酶的伴侣蛋白。在这次审查中,我专注于这些tRNA修饰酶的功能和结构以及它们产生的修饰核苷。生物化学,tRNA4-硫尿苷合成酶的生物物理和结构研究,tRNA甲基转移酶和tRNA脱氨酶已经确立了THUMP结构域捕获RNA的3'-末端的概念(在tRNA的情况下,CCA终点)。然而,在某些情况下,考虑到在tRNA中观察到的修饰模式,这个概念并不简单适用.此外,THUMP相关蛋白参与其他RNA以及tRNA的成熟。此外,修饰的核苷,由THUMP相关的tRNA修饰酶产生,涉及许多生物现象,人类THUMP相关蛋白的基因缺陷与遗传疾病有关。在这次审查中,还介绍了这些生物学现象。
The existence of the thiouridine synthetase, methyltransferase and pseudouridine synthase (THUMP) domain was originally predicted by a bioinformatic study. Since the prediction of the THUMP domain more than two decades ago, many tRNA modification enzymes containing the THUMP domain have been identified. According to their enzymatic activity, THUMP-related tRNA modification enzymes can be classified into five types, namely 4-thiouridine synthetase, deaminase, methyltransferase, a partner protein of acetyltransferase and pseudouridine synthase. In this review, I focus on the functions and structures of these tRNA modification enzymes and the modified nucleosides they produce. Biochemical, biophysical and structural studies of tRNA 4-thiouridine synthetase, tRNA methyltransferases and tRNA deaminase have established the concept that the THUMP domain captures the 3\'-end of RNA (in the case of tRNA, the CCA-terminus). However, in some cases, this concept is not simply applicable given the modification patterns observed in tRNA. Furthermore, THUMP-related proteins are involved in the maturation of other RNAs as well as tRNA. Moreover, the modified nucleosides, which are produced by the THUMP-related tRNA modification enzymes, are involved in numerous biological phenomena, and the defects of genes for human THUMP-related proteins are implicated in genetic diseases. In this review, these biological phenomena are also introduced.