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Issue 10, 2015
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Metal binding spectrum and model structure of the Bacillus anthracis virulence determinant MntA

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Abstract

The potentially lethal human pathogen Bacillus anthracis expresses a putative metal import system, MntBCA, which belongs to the large family of ABC transporters. MntBCA is essential for virulence of Bacillus anthracis: deletion of MntA, the system's substrate binding protein, yields a completely non-virulent strain. Here we determined the metal binding spectrum of MntA. In contrast to what can be inferred from growth complementation studies we find no evidence that MntA binds Fe2+ or Fe3+. Rather, MntA binds a variety of other metal ions, including Mn2+, Zn2+, Cd2+, Co2+, and Ni2+ with affinities ranging from 10−6 to 10−8 M. Binding of Zn2+ and Co2+ have a pronounced thermo-stabilizing effect on MntA, with Mn2+ having a milder effect. The thermodynamic stability of MntA, competition experiments, and metal binding and release experiments all suggest that Mn2+ is the metal that is likely transported by MntBCA and is therefore the limiting factor for virulence of Bacillus anthracis. A homology-model of MntA shows a single, highly conserved metal binding site, with four residues that participate in metal coordination: two histidines, a glutamate, and an aspartate. The metals bind to this site in a mutually exclusive manner, yet surprisingly, mutational analysis shows that for proper coordination each metal requires a different subset of these four residues. ConSurf evolutionary analysis and structural comparison of MntA and its homologues suggest that substrate binding proteins (SBPs) of metal ions use a pair of highly conserved prolines to interact with their cognate ABC transporters. This proline pair is found exclusively in ABC import systems of metal ions.

Graphical abstract: Metal binding spectrum and model structure of the Bacillus anthracis virulence determinant MntA

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Publication details

The article was received on 11 Apr 2015, accepted on 16 Jun 2015 and first published on 16 Jun 2015


Article type: Paper
DOI: 10.1039/C5MT00100E
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Citation: Metallomics, 2015,7, 1407-1419
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    Metal binding spectrum and model structure of the Bacillus anthracis virulence determinant MntA

    E. Vigonsky, I. Fish, N. Livnat-Levanon, E. Ovcharenko, N. Ben-Tal and O. Lewinson, Metallomics, 2015, 7, 1407
    DOI: 10.1039/C5MT00100E

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