Structure of an as(III) S -adenosylmethionine methyltransferase

Insights into the mechanism of arsenic biotransformation

A. Abdul Ajees, Kavitha Marapakala, Charles Packianathan, Banumathi Sankaran, Barry P. Rosen

Research output: Contribution to journalArticle

60 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5476-5485
Number of pages10
JournalBiochemistry
Volume51
Issue number27
DOIs
Publication statusPublished - 10-07-2012

Fingerprint

S-Adenosylmethionine
Methyltransferases
Arsenic
Biotransformation
Metalloids
Detoxification
Methylation
X ray crystallography
X Ray Crystallography
Algae
Polymorphism
Catalysis
Microorganisms
Conformations
Oxidoreductases
Binding Sites
Substrates

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Ajees, A. Abdul ; Marapakala, Kavitha ; Packianathan, Charles ; Sankaran, Banumathi ; Rosen, Barry P. / Structure of an as(III) S -adenosylmethionine methyltransferase : Insights into the mechanism of arsenic biotransformation. In: Biochemistry. 2012 ; Vol. 51, No. 27. pp. 5476-5485.
@article{038dd240d6dd4f0fbf4da7a779cca3a0,
title = "Structure of an as(III) S -adenosylmethionine methyltransferase: Insights into the mechanism of arsenic biotransformation",
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 {\AA}. 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.",
author = "Ajees, {A. Abdul} and Kavitha Marapakala and Charles Packianathan and Banumathi Sankaran and Rosen, {Barry P.}",
year = "2012",
month = "7",
day = "10",
doi = "10.1021/bi3004632",
language = "English",
volume = "51",
pages = "5476--5485",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "27",

}

Structure of an as(III) S -adenosylmethionine methyltransferase : Insights into the mechanism of arsenic biotransformation. / Ajees, A. Abdul; Marapakala, Kavitha; Packianathan, Charles; Sankaran, Banumathi; Rosen, Barry P.

In: Biochemistry, Vol. 51, No. 27, 10.07.2012, p. 5476-5485.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Structure of an as(III) S -adenosylmethionine methyltransferase

T2 - Insights into the mechanism of arsenic biotransformation

AU - Ajees, A. Abdul

AU - Marapakala, Kavitha

AU - Packianathan, Charles

AU - Sankaran, Banumathi

AU - Rosen, Barry P.

PY - 2012/7/10

Y1 - 2012/7/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84863740521&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863740521&partnerID=8YFLogxK

U2 - 10.1021/bi3004632

DO - 10.1021/bi3004632

M3 - Article

VL - 51

SP - 5476

EP - 5485

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 27

ER -