6cx6

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

spinqualitylabelsall models 6cx6, resolution 2.84Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6cx6 is a 2 chain structure with sequence from Cyanidioschyzon sp. 5508. This structure supersedes the now removed PDB entry 5jwn. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ARS, SAH Gene: arsM (Cyanidioschyzon sp. 5508) Activity: Arsenite methyltransferase, with EC number 2.1.1.137 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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. The Structure of an As(III) S-Adenosylmethionine Methyltransferase with 3-Coordinately Bound As(III) Depicts the First Step in Catalysis.,Packianathan C, Kandavelu P, Rosen BP Biochemistry. 2018 Jun 26. doi: 10.1021/acs.biochem.8b00457. PMID:29894638 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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