Proposed mechanism for monomethylarsonate reductase activity of human omega-class glutathione transferase GSTO1-1
Publication Name
Biochemical and Biophysical Research Communications
Abstract
Contamination of drinking water with toxic inorganic arsenic is a major public health issue. The mechanisms of enzymes and transporters in arsenic elimination are therefore of interest. The human omega-class glutathione transferases have been previously shown to possess monomethylarsonate (V) reductase activity. To further understanding of this activity, molecular dynamics of human GSTO1-1 bound to glutathione with a monomethylarsonate isostere were simulated to reveal putative monomethylarsonate binding sites on the enzyme. The major binding site is in the active site, adjacent to the glutathione binding site. Based on this and previously reported biochemical data, a reaction mechanism for this enzyme is proposed. Further insights were gained from comparison of the human omega-class GSTs to homologs from a range of animals.
Open Access Status
This publication may be available as open access
Volume
590
First Page
7
Last Page
13
Funding Number
R01-GM129325
Funding Sponsor
National Institutes of Health