4FS8

The structure of an As(III) S-adenosylmethionine methyltransferase: insights into the mechanism of arsenic biotransformation

「3P7E」から置き換えられました

4FS8 の概要

• エントリーDOI: 10.2210/pdb4fs8/pdb
• 関連するPDBエントリー: 4FR0 4FSD
• 分子名称: Arsenic methyltransferase, CALCIUM ION (3 entities in total)
• 機能のキーワード: rossmann fold, arsenic methyltransferase, transferase
• 由来する生物種: Cyanidioschyzon sp. 5508
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42352.81

構造登録者

Ajees, A.A.,Marapakala, K.,Packianathan, C.,Sankaran, B.,Rosen, B.P. (登録日: 2012-06-27, 公開日: 2012-07-11, 最終更新日: 2024-02-28)

主引用文献

Ajees, A.A.,Marapakala, K.,Packianathan, C.,Sankaran, B.,Rosen, B.P.
Structure of an As(III) S-Adenosylmethionine Methyltransferase: Insights into the Mechanism of Arsenic Biotransformation.
Biochemistry, 51:5476-5485, 2012

PubMed Abstract: Enzymatic methylation of arsenic is a detoxification process in microorganisms but in humans may activate the metalloid to more carcinogenic species. We describe the first structure of an As(III) S-adenosylmethionine methyltransferase by X-ray crystallography that reveals a novel As(III) binding domain. The structure of the methyltransferase from the thermophilic eukaryotic alga Cyanidioschyzon merolae reveals the relationship between the arsenic and S-adenosylmethionine binding sites to a final resolution of ∼1.6 Å. As(III) binding causes little change in conformation, but binding of SAM reorients helix α4 and a loop (residues 49-80) toward the As(III) binding domain, positioning the methyl group for transfer to the metalloid. There is no evidence of a reductase domain. These results are consistent with previous suggestions that arsenic remains trivalent during the catalytic cycle. A homology model of human As(III) S-adenosylmethionine methyltransferase with the location of known polymorphisms was constructed. The structure provides insights into the mechanism of substrate binding and catalysis.

PubMed: 22712827
DOI: 10.1021/bi3004632

実験手法

X-RAY DIFFRACTION (1.78 Å)