Mechanism of metal-ion activation

Site-directed mutagenesis of DtxR has indicated that, of the two metal-ion binding sites identified earlier, only one is essential for repressor activity [22, 27, 31]. Individual mutation of Met 10, Cys 102, Glu 105 or His 106, the primary metal-ion binding ligands, to Ala resulted in non-fimctional repressors [22, 31]. Individual mutation of residues His 79, Glu 83 or His 98, the ligands to the ancillary site, to Ala resulted in still functional repressors [22]. The implication of these studies is that one of the metal-ion binding sites is essential to repressor activity, while the other is not, or has at best a modulatory function. 

The crystal structure of metal-ion activated DtxR suggests two, mutually nonexclusive, models for the mechanism of activation of this repressor. Comparison of the apo- and holo-repressors shows a conformational change between the two sub- 

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D Aquino JA, Tetenbaum- Novatt J, White A, Berkovitch F, Ringe D. Mechanism of metal ion activation of the diphtheria toxin repressor DtxR. Proc. Natl. Acad. Sci. U.S.A. 2005 102 18408-18413. 

Spencer SG, Brewer JM, Ellis PD (1985) Cadmium(II)-113 NMR studies of the mechanism of metal ion activation of yeast enolase. J Inorg Biochem 24(l) 47-57. 

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