Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida 33199, United States.
Environ Sci Technol. 2023 Jul 4;57(26):9754-9761. doi: 10.1021/acs.est.3c00966. Epub 2023 Jun 16.
Arsenic is methylated by arsenite (As(III)) -adenosylmethionine (SAM) methyltransferases (ArsMs). ArsM crystal structures show three domains (an N-terminal SAM binding domain (A domain), a central arsenic binding domain (B domain), and a C-terminal domain of unknown function (C domain)). In this study, we performed a comparative analysis of ArsMs and found a broad diversity in structural domains. The differences in the ArsM structure enable ArsMs to have a range of methylation efficiencies and substrate selectivities. Many small ArsMs with 240-300 amino acid residues have only A and B domains, represented by RpArsM from . These small ArsMs have higher methylation activity than larger ArsMs with 320-400 residues such as CrArsM, which has A, B, and C domains. To examine the role of the C domain, the last 102 residues in CrArsM were deleted. This CrArsM truncation exhibited higher As(III) methylation activity than the wild-type enzyme, suggesting that the C-terminal domain has a role in modulating the rate of catalysis. In addition, the relationship of arsenite efflux systems and methylation was examined. Lower rates of efflux led to higher rates of methylation. Thus, the rate of methylation can be modulated in multiple ways.
砷通过亚砷酸盐（As(III)）-腺苷甲硫氨酸（SAM）甲基转移酶（ArsMs）进行甲基化。ArsM 晶体结构显示三个结构域（N 端 SAM 结合结构域（A 结构域）、中心砷结合结构域（B 结构域）和功能未知的 C 端结构域（C 结构域））。在这项研究中，我们对 ArsMs 进行了比较分析，发现其结构域存在广泛的多样性。ArsM 结构的差异使 ArsMs 具有不同的甲基化效率和底物选择性。许多具有 240-300 个氨基酸残基的小 ArsMs 仅具有 A 和 B 结构域，以. 中的 RpArsM 为代表。这些小 ArsMs 的甲基化活性高于具有 320-400 个残基的较大 ArsMs，如具有 A、B 和 C 结构域的 CrArsM。为了研究 C 结构域的作用，我们删除了 CrArsM 中的最后 102 个残基。该 CrArsM 截断酶表现出比野生型酶更高的 As(III)甲基化活性，表明 C 端结构域在调节催化速率方面发挥作用。此外，还研究了亚砷酸盐外排系统与甲基化的关系。较低的外排速率导致更高的甲基化速率。因此，甲基化的速率可以通过多种方式进行调节。
