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人砷(III)-S-腺苷甲硫氨酸甲基转移酶(hAS3MT)的纯化、结晶及初步晶体学研究

Purification, Crystallization, and Preliminary Crystallographic Studies of Human As(III) S-Adenosylmethionine Methyltransferase (hAS3MT).

作者信息

Radhakrishnan M, Packianathan C, Sankaran B, Kandavelu P, Rosen B P

机构信息

Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL.33199 USA.

Department of Chemistry, Texas A&M University, College Station, Texas, TX USA.

出版信息

Crystallogr Rep. 2021 Dec;66(7):1311-1315. doi: 10.1134/s1063774521070129. Epub 2021 Dec 14.

Abstract

Exposure to environmental arsenic is associated with serious of health issues such as cancer, diabetes and developmental delays in infants and children. In human liver, As(III) S-adenosylmethionine methyl transferase (hAS3MT) (EC 2.1.1.137) was proposed to be an detoxification process by methylation of inorganic arsenite into pentavalent methyl MAs(V) and dimethyl arsenite DMAs(V). More recently the first product was shown to be highly toxic and potentially carcinogenic trivalent methylarsenite (MAs(III)). Our studies are designed to elucidate the mechanism of AS3MT and its contribution to arsenic-related diseases. Here, we report the first crystallization and preliminary X-ray diffraction analysis of the human AS3MT enzyme. The crystals belong to the monoclinic 121 space group with unit cell parameters of = 135.03 Å, = 260.44 Å, = 279.03 Å, α = 90.00°, β = 93.36°, γ = 90.00°.

摘要

接触环境中的砷与多种严重健康问题相关,如癌症、糖尿病以及婴幼儿发育迟缓。在人类肝脏中,三价砷S-腺苷甲硫氨酸甲基转移酶(hAS3MT)(EC 2.1.1.137)被认为是通过将无机亚砷酸盐甲基化为五价甲基砷(MAs(V))和二甲基亚砷酸盐(DMAs(V))来进行解毒的过程。最近研究表明,第一种产物是剧毒且具有潜在致癌性的三价甲基亚砷酸盐(MAs(III))。我们的研究旨在阐明AS3MT的作用机制及其对砷相关疾病的影响。在此,我们报告了人类AS3MT酶的首次结晶及初步X射线衍射分析。晶体属于单斜晶系121空间群,晶胞参数为 = 135.03 Å, = 260.44 Å, = 279.03 Å,α = 90.00°,β = 93.36°,γ = 90.00°。

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Earth Abides Arsenic Biotransformations.《大地长存:砷的生物转化》
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Pathway of human AS3MT arsenic methylation.人类砷甲基转移酶(AS3MT)的砷甲基化途径。
Chem Res Toxicol. 2014 Nov 17;27(11):1979-89. doi: 10.1021/tx500313k. Epub 2014 Oct 30.
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