title: Molecular basis of bacterial resistance to organomercurial and inorganic mercuric salts.
abstract: Bacteria mediate resistance to organomercurial and inorganic mercuric salts by metabolic conversion to nontoxic elemental mercury, Hg(0). The genes responsible for mercury resistance are organized in the mer operon, and such operons are often found in plasmids that also bear drug resistance determinants. We have subcloned three of these mer genes, merR, merB, and merA, and have studied their protein products via protein overproduction and purification, and structural and functional characterization. MeR is a metalloregulatory DNA-binding protein that acts as a repressor of both its own and structural gene transcription in the absence of Hg(II); in addition it acts as a positive effector of structural gene transcription when Hg(II) is present. MerB, organomercury lyase, catalyzes the protonolytic fragmentation of organomercurials to the parent hydrocarbon and Hg(II) by an apparent SE2 mechanism. MerA, mercuric ion reductase, is an FAD-containing and redox-active disulfide-containing enzyme with homology to glutathione reductase. It has evolved the unique catalytic capacity to reduce Hg(II) to Hg(0) and thereby complete the detoxification scheme.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: C T
authors.initials: CT
authors.lastname: Walsh
authors.forename: M D
authors.initials: MD
authors.lastname: Distefano
authors.forename: M J
authors.initials: MJ
authors.lastname: Moore
authors.forename: L M
authors.initials: LM
authors.lastname: Shewchuk
authors.forename: G L
authors.initials: GL
authors.lastname: Verdine
mesh_terms: D001419:Bacteria / Q000187:drug effects* / Q000235:genetics; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism; D004352:Drug Resistance, Microbial; D005796:Genes; D005798:Genes, Bacterial; D008628:Mercury / Q000494:pharmacology*; D008958:Models, Molecular; D009154:Mutation; D009876:Operon; D009941:Organomercury Compounds / Q000494:pharmacology*
chemical_list: D004268:DNA-Binding Proteins; D009941:Organomercury Compounds; D008628:Mercury