Abstract
A newly identified bacterial strain that can grow in the presence of arsenate and possibly in the absence of phosphate, has raised much interest, but also fueled an active debate. Can arsenate substitute for phosphate in some or possibly in most of the absolutely essential phosphate-based biomolecules, including DNA? If so, then the possibility of alternative, arsenic-based life forms must be considered. The physicochemical similarity of these two oxyanions speaks in favor of this idea. However, arsenate-esters and arsenate-diesters in particular are extremely unstable in aqueous media. Here, we explore the potential of arsenate to be used as substrate by phosphate-utilizing enzymes. We review the existing literature on arsenate enzymology, that intriguingly, dates back to the 1930s. We address the issue of how and to what degree proteins can distinguish between arsenate and phosphate and what is known in general about oxyanion specificity. We also discuss how phosphate-arsenate promiscuity may affect evolutionary transitions between phosphate- and arsenate-based biochemistry. Finally, we highlight potential applications of arsenate as a structural and mechanistic probe of enzymes whose catalyzed reactions involve the making or breaking of phosphoester bonds.