title: Synergistic interaction of glyceraldehydes-3-phosphate dehydrogenase and ArsJ, a novel organoarsenical efflux permease, confers arsenate resistance.
abstract: Microbial biotransformations are major contributors to the arsenic biogeocycle. In parallel with transformations of inorganic arsenic, organoarsenicals pathways have recently been recognized as important components of global cycling of arsenic. The well-characterized pathway of resistance to arsenate is reduction coupled to arsenite efflux. Here, we describe a new pathway of arsenate resistance involving biosynthesis and extrusion of an unusual pentavalent organoarsenical. A number of arsenic resistance (ars) operons have two genes of unknown function that are linked in these operons. One, gapdh, encodes the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase. The other, arsJ, encodes a major facilitator superfamily (MFS) protein. The two genes were cloned from the chromosome of Pseudomonas aeruginosa. When expressed together, but not alone, in Escherichia coli, gapdh and arsJ specifically conferred resistance to arsenate and decreased accumulation of As(V). Everted membrane vesicles from cells expressing arsJ accumulated As(V) in the presence of purified GAPDH, D-glceraldehylde 3-phosphate (G3P) and NAD(+) . GAPDH forms the unstable organoarsenical 1-arseno-3-phosphoglycerate (1As3PGA). We propose that ArsJ is an efflux permease that extrudes 1As3PGA from cells, where it rapidly dissociates into As(V) and 3-phosphoglycerate (3PGA), creating a novel pathway of arsenate resistance.
authors.affiliation: Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yoshinaga
authors.affiliation: Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA.
authors.forename: Luis D
authors.initials: LD
authors.lastname: Garbinski
authors.affiliation: Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA.
authors.forename: Barry P
authors.initials: BP
authors.lastname: Rosen
mesh_terms: D001149:Arsenates / Q000378:metabolism* / Q000633:toxicity; D001151:Arsenic / Q000378:metabolism; D018053:Arsenites / Q000378:metabolism*; D001192:Arylsulfatases / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D004351:Drug Resistance; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D009876:Operon; D010710:Phosphates / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000378:metabolism
chemical_list: D001149:Arsenates; D018053:Arsenites; D001426:Bacterial Proteins; D009097:Multienzyme Complexes; D010710:Phosphates; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D001192:Arylsulfatases; C015001:arsenite; D001151:Arsenic; C025657:arsenic acid