4FSD

ArsM arsenic(III) S-adenosylmethionine methyltransferase with As(III)

Replaces:  3QNH

Summary for 4FSD

• Entry DOI: 10.2210/pdb4fsd/pdb
• Related: 4FR0 4FS8
• Descriptor: Arsenic methyltransferase, ARSENIC, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: rossmann fold, arsenic methyltransferase, transferase
• Biological source: Cyanidioschyzon sp. 5508
• Total number of polymer chains: 1
• Total formula weight: 42503.26

Authors

Ajees, A.A.,Marapakala, K.,Packianathan, C.,Sankaran, B.,Rosen, B.P. (deposition date: 2012-06-27, release date: 2012-07-11, Last modification date: 2023-09-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.75 Å)