Functional evaluation of Asp76, 84, 102 and 150 in human arsenic(III) methyltransferase (hAS3MT) interacting with S-adenosylmethionine

FEBS Lett. 2013 Jul 11;587(14):2232-40. doi: 10.1016/j.febslet.2013.05.052. Epub 2013 Jun 4.

Abstract

We prepared eight mutants (D76P, D76N, D84P, D84N, D102P, D102N, D150P and D150N) to investigate the functions of residues Asp76, 84, 102 and 150 in human arsenic(III) methyltransferase (hAS3MT) interacting with the S-adenosylmethionine (SAM)-binding. The affinity of all the mutants for SAM were weakened. All the mutants except for D150N completely lost their methylation activities. Residues Asp76, 84, 102 and 150 greatly influenced hAS3MT catalytic activity via affecting SAM-binding or methyl transfer. Asp76 and 84 were located in the SAM-binding pocket, and Asp102 significantly affected SAM-binding via forming hydrogen bonds with SAM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution*
  • Arsenic / chemistry
  • Catalytic Domain
  • Circular Dichroism
  • Humans
  • Hydrogen Bonding
  • Kinetics
  • Methylation
  • Methyltransferases / chemistry*
  • Methyltransferases / genetics
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Protein Binding
  • Protein Structure, Secondary
  • S-Adenosylmethionine / chemistry*
  • Spectroscopy, Fourier Transform Infrared

Substances

  • S-Adenosylmethionine
  • Methyltransferases
  • AS3MT protein, human
  • Arsenic