Metalloid resistance mechanisms in prokaryotes.
Resistance to antibiotics and other chemotherapeutic agents is becoming a wide spread health issue. The biochemical mechanisms of resistance vary, but active efflux of the toxic agents is one of the most common. Bacterial resistances to metals provide good model systems for transport-related resistances. One of the best understood metal resistance systems is the product of the ars operon, which provides resistance to arsenicals and antimonials. As a reflection of the ubiquity of arsenic in the environment, ars operons are found in all species of bacteria, carried in chromosomes, plasmids, and transposons. This review focuses on the biochemistry of the proteins of the ars operon of R-factor R773. The system is novel in several respects. First, it is regulated at the transcriptional and allosteric levels, and regulation is effected through cysteine thiol interaction with As(III) or Sb(III). Thus soft metal-thiol chemistry provides a high affinity digital switch to turn the regulated protein on with rapidity. The transport system that provides resistance, on the other hand, uses oxyanions of arsenic or antimony as substrates. This nonmetal chemistry allows for low affinity interactions of the membrane transporter with substrate, conductive with translocation and release of substrate on the outside of the cell membrane. Second, the transporter is uniquely capable of coupling to either electrochemical energy as a secondary carrier protein or the chemical energy of ATP when binding of a catalytic subunit converts it into an anion-translocating ATPase.
Xu
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Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Zhou
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T
Kuroda
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Rosen
B P
BP
D000251:Adenosine Triphosphatases / Q000737:chemistry*; D000595:Amino Acid Sequence; D000965:Antimony / Q000494:pharmacology; D001152:Arsenicals / Q000494:pharmacology*; D053501:Arsenite Transporting ATPases; D004352:Drug Resistance, Microbial; D016623:Ion Pumps; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes; D011387:Prokaryotic Cells; D011815:R Factors
D001152:Arsenicals; D016623:Ion Pumps; D009097:Multienzyme Complexes; D000965:Antimony; D000251:Adenosine Triphosphatases; D053501:Arsenite Transporting ATPases