S- adenosyl- L- methionine is the unexpected methyl donor for the methylation of mercury by the membrane- associated HgcAB complex

• 成果类型: Article
• 署名作者: Zheng, Kaiyuan; Rush, Katherine W.; Date, Swapneeta S.; Johs, Alexander; Parks, Jerry M.; Fleischhacker, Angela S.; Abernathy, Macon J.; Sarangi, Ritimukta; Ragsdale, Stephen W.
• 署名单位: University of Michigan System; University of Michigan; United States Department of Energy (DOE); Oak Ridge National Laboratory; United States Department of Energy (DOE); Oak Ridge National Laboratory; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; University of Virginia; Auburn University System; Auburn University; Vanderbilt University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10632
• DOI: 10.1073/pnas.2408086121
• 发表日期: 2024-11-19
• 关键词: acetyl-coenzyme; escherichia-coli; radical sam; methyltransferase; PATHWAY; fom3; gentamicin; activation; mechanism; catalysis

摘要

Mercury (Hg) is a heavy metal that exhibits high biological toxicity. Monomethylmercury and dimethylmercury are neurotoxins and a significant environmental concern as they bioaccumulate and biomagnify within the aquatic food web. Microbial Hg methylation involves two proteins, HgcA and HgcB. Here, we show that HgcA and HgcB can be heterologously coexpressed, and the HgcAB complex can be purified. We demonstrated that HgcA is a membrane- associated cobalamin- dependent methyltransferase and HgcB is a ferredoxin-like protein containing two [4Fe-4S] clusters. Further, spectroscopic and kinetic results demonstrate that S- adenosyl- L- methionine (SAM) donates the methyl group to Hg in a two- step reaction involving a methylcob(III)alamin intermediate including Co- thiolate ligation from a conserved Cys residue. Our findings uncover a biological role for SAM in microbial Hg methylation.