6CX6

The structure of an As(III) S-adenosylmethionine methyltransferase with As(III) and S-adenosyl-L-homocysteine (SAH)

「5JWN」から置き換えられました

6CX6 の概要

• エントリーDOI: 10.2210/pdb6cx6/pdb
• 分子名称: Arsenic methyltransferase, S-ADENOSYL-L-HOMOCYSTEINE, ARSENIC, ... (4 entities in total)
• 機能のキーワード: methyltransferase, transferase
• 由来する生物種: Cyanidioschyzon sp. 5508
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 84519.02

構造登録者

Packianathan, C.,Kandavelu, P.,Rosen, B.P. (登録日: 2018-04-02, 公開日: 2018-06-27, 最終更新日: 2023-10-04)

主引用文献

Packianathan, C.,Kandavelu, P.,Rosen, B.P.
The Structure of an As(III) S-Adenosylmethionine Methyltransferase with 3-Coordinately Bound As(III) Depicts the First Step in Catalysis.
Biochemistry, 57:4083-4092, 2018

PubMed Abstract: Arsenic is a ubiquitous environmental toxic substance and a Class 1 human carcinogen. Arsenic methylation by the enzyme As(III) S-adenosylmethionine (SAM) methyltransferase (ArsM in microbes or AS3MT in animals) detoxifies As(III) in microbes but transforms it into more toxic and potentially more carcinogenic methylated species in humans. We previously proposed a reaction pathway for ArsM/AS3MT that involves initial 3-coordinate binding of As(III). To date, reported structures have had only 2-coordinately bound trivalent arsenicals. Here we report a crystal structure of CmArsM from Cyanidioschyzon sp.5508 in which As(III) is 3-coordinately bound to three conserved cysteine residues with a molecule of the product S-adenosyl-l-homocysteine bound in the SAM binding site. We propose that this structure represents the first step in the catalytic cycle. In a previously reported SAM-bound structure, a disulfide bond is formed between two conserved cysteine residues. Comparison of these two structures indicates that there is a conformational change in the N-terminal domain of CmArsM that moves a loop to allow formation of the 3-coordinate As(III) binding site. We propose that this conformational change is an initial step in the As(III) SAM methyltransferase catalytic cycle.

PubMed: 29894638
DOI: 10.1021/acs.biochem.8b00457

実験手法

X-RAY DIFFRACTION (2.84 Å)