Mikael Elias Alon Wellner Korina Goldin-Azulay Eric Chabriere Julia A. Vorholt Tobias J. Erb & Dan S. Tawfik. The molecular basis of phosphate discrimination in arsenate-rich environments. Nature 2012 491: 134–137. doi:10.1038-nature11517.
Abstract
Arsenate and phosphate are abundant on Earth and have striking similarities: nearly identical pKa values1 2 similarly charged oxygen atoms and thermochemical radii that differ by only 4% (ref. 3). Phosphate is indispensable and arsenate is toxic but this extensive similarity raises the question whether arsenate may substitute for phosphate in certain niches4 5. However whether it is used or excluded discriminating phosphate from arsenate is a paramount challenge. Enzymes that utilize phosphate for example have the same binding mode and kinetic parameters as arsenate and the latter|[rsquo]|s presence therefore decouples metabolism6 7. Can proteins discriminate between these two anions and how would they do so? In particular cellular phosphate uptake systems face a challenge in arsenate-rich environments. Here we describe a molecular mechanism for this process. We examined the periplasmic phosphate-binding proteins (PBPs) of the ABC-type transport system that mediates phosphate uptake into bacterial cells including two PBPs from the arsenate-rich Mono Lake Halomonas strain GFAJ-1. All PBPs tested are capable of discriminating phosphate over arsenate at least 500-fold. The exception is one of the PBPs of GFAJ-1 that shows roughly 4500-fold discrimination and its gene is highly expressed under phosphate-limiting conditions. Sub-|[aring]|ngstr|[ouml]|m-resolution structures of Pseudomonas fluorescens PBP with both arsenate and phosphate show a unique mode of binding that mediates discrimination. An extensive network of dipole|[ndash]|anion interactions8
