Arsenite Methyltransferase Diversity and Optimization of Methylation Efficiency

Here,we illustrate the broad diversity of the structuraldomains and arsenic binding sites in As(III) S-adenosylmethioninemethyltransferases (ArsMs). Our results suggest that a C-terminaldomain evolved for production of complex organoarsenicals. Arsenic is methylated by arsenite (As(III)) S-adenosylmethionine(SAM) methyltransferases (ArsMs). ArsM crystal structures show threedomains (an N-terminal SAM binding domain (A domain), a central arsenicbinding domain (B domain), and a C-terminal domain of unknown function(C domain)). In this study, we performed a comparative analysis ofArsMs and found a broad diversity in structural domains. The differencesin the ArsM structure enable ArsMs to have a range of methylationefficiencies and substrate selectivities. Many small ArsMs with 240-300amino acid residues have only A and B domains, represented by RpArsMfrom Rhodopseudomonas palustris. Thesesmall ArsMs have higher methylation activity than larger ArsMs with320-400 residues such as Chlamydomonas reinhardtii CrArsM, which has A, B, and C domains. To examine the role of theC domain, the last 102 residues in CrArsM were deleted. This CrArsMtruncation exhibited higher As(III) methylation activity than thewild-type enzyme, suggesting that the C-terminal domain has a rolein modulating the rate of catalysis. In addition, the relationshipof arsenite efflux systems and methylation was examined. Lower ratesof efflux led to higher rates of methylation. Thus, the rate of methylationcan be modulated in multiple ways.

Automated summary

In this study, the broad diversity of structural domains in ArsMs was revealed through comparative analysis. The differences in the ArsM structure lead to variations in methylation efficiency and substrate selectivity. The C-terminal domain was found to play a role in modulating the rate of catalysis. Additionally, the relationship between arsenite efflux systems and methylation was examined.