A new family of periplasmic-binding proteins that sense arsenic oxyanions

Abstract

Arsenic contamination of drinking water affects more than 140 million people worldwide. While toxic to humans, inorganic forms of arsenic (arsenite and arsenate), can be used as energy sources for microbial respiration. AioX and its orthologues (ArxX and ArrX) represent the first members of a new sub-family of periplasmic-binding proteins that serve as the first component of a signal transduction system, that’s role is to positively regulate expression of arsenic metabolism enzymes. As determined by X-ray crystallography for AioX, arsenite binding only requires subtle conformational changes in protein structure, providing insights into protein-ligand interactions. The binding pocket of all orthologues is conserved but this alone is not sufficient for oxyanion selectivity, with proteins selectively binding either arsenite or arsenate. Phylogenetic evidence, clearly demonstrates that the regulatory proteins evolved together early in prokaryotic evolution and had a separate origin from the metabolic enzymes whose expression they regulate.

Arsenite Oxidation by a Newly Isolated Betaproteobacterium Possessing arx Genes and Diversity of the arx Gene Cluster in Bacterial Genomes

“…The arxXSR genes are absent from the arx gene cluster of the genomes from members of the order Oceanospirillales (Figure 4). Similar findings were reported in previous studies on the gene clusters of aio and arr , which indicated that the presence of aioXSR and arrXSR is variable among taxonomic groups (Slyemi and Bonnefoy, 2012; Van Lis et al, 2013; Badilla et al, 2018). The aioXSR genes regulate the expression of the aioAB genes in some arsenite-oxidizing strains (Kashyap et al, 2006; Koechler et al, 2010; Sardiwal et al, 2010; Liu et al, 2012; Li et al, 2013).…”

“…Comparison among amino acid sequences of the ArxAB encoded in the identified genomes indicated that they share some characteristics with those of A. ehrlichii MLHE-1 and Ectothiorhodospira sp. PHS-1 reported in previous studies (Zargar et al, 2010, 2012; Van Lis et al, 2013; Badilla et al, 2018), as described below. The ArxA sequences had three conserved regions commonly identified in subunit A of the DMSO reductase family enzymes: an iron–sulfur [4Fe-4S] motif; a catalytic binding pocket sequence similar to that suggested in the ArxA of A. ehrlichii MLHE-1 and Ectothiorhodospira sp.…”

ArxA From Azoarcus sp. CIB, an Anaerobic Arsenite Oxidase From an Obligate Heterotrophic and Mesophilic Bacterium

“…It is assumed that the regulator AioR does not interact directly with arsenite, is one component of the signal transduction that involves AioX that binds arsenite at periplasm, and the histidine-kinase AioS that transfer the information from the periplasm to the cytoplasm (Kashyap et al, 2006; Saltikov, 2011). It is possible that this scheme is also present in CIB strain with the component of the arx cluster, being ArxX protein the periplasmic arsenite binding protein (Badilla et al, 2018), ArxS the sensor kinase responsible for the information transduction to the cytoplasm, and ArxR the response regulator that sense the signal transferred by ArxS. Further experiments about this subject are required to establish the complete network of regulation of the arx genes in Azoarcus sp.…”

Structural and Functional Investigation of the Periplasmic Arsenate-Binding Protein ArrX from Chrysiogenes arsenatis

“…Crucially, the binding of AsO4 3to the AioX protein and AsO3 3to the ArrX protein could not be detected 46 , indicating significant specificity of these two PBPs for their respective substrates.…”