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Evolution of metal(loid) binding sites in transcriptional regulators.

ABSTRACT: Expression of the genes for resistance to heavy metals and metalloids is transcriptionally regulated by the toxic ions themselves. Members of the ArsR/SmtB family of small metalloregulatory proteins respond to transition metals, heavy metals, and metalloids, including As(III), Sb(III), Cd(II), Pb(II), Zn(II), Co(II), and Ni(II). These homodimeric repressors bind to DNA in the absence of inducing metal(loid) ion and dissociate from the DNA when inducer is bound. The regulatory sites are often three- or four-coordinate metal binding sites composed of cysteine thiolates. Surprisingly, in two different As(III)-responsive regulators, the metalloid binding sites were in different locations in the repressor, and the Cd(II) binding sites were in two different locations in two Cd(II)-responsive regulators. We hypothesize that ArsR/SmtB repressors have a common backbone structure, that of a winged helix DNA-binding protein, but have considerable plasticity in the location of inducer binding sites. Here we show that an As(III)-responsive member of the family, CgArsR1 from Corynebacterium glutamicum, binds As(III) to a cysteine triad composed of Cys(15), Cys(16), and Cys(55). This binding site is clearly unrelated to the binding sites of other characterized ArsR/SmtB family members. This is consistent with our hypothesis that metal(loid) binding sites in DNA binding proteins evolve convergently in response to persistent environmental pressures.

SUBMITTER: Ordonez E

PROVIDER: S-EPMC2533085 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Evolution of metal(loid) binding sites in transcriptional regulators.

Ordóñez Efrén E Thiyagarajan Saravanamuthu S Cook Jeremy D JD Stemmler Timothy L TL Gil José A JA Mateos Luís M LM Rosen Barry P BP

The Journal of biological chemistry 20080630 37

Expression of the genes for resistance to heavy metals and metalloids is transcriptionally regulated by the toxic ions themselves. Members of the ArsR/SmtB family of small metalloregulatory proteins respond to transition metals, heavy metals, and metalloids, including As(III), Sb(III), Cd(II), Pb(II), Zn(II), Co(II), and Ni(II). These homodimeric repressors bind to DNA in the absence of inducing metal(loid) ion and dissociate from the DNA when inducer is bound. The regulatory sites are often thr ...[more]

PMID: 18591244

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Dataset Information

Evolution of metal(loid) binding sites in transcriptional regulators.

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Evolution of metal(loid) binding sites in transcriptional regulators.

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