Structure of the metal-ion-activated diphtheria toxin repressor/ tox operator complex

Nature ◽  
10.1038/28893 ◽  
1998 ◽  
Vol 394 (6692) ◽  
pp. 502-506 ◽  
Author(s):  
André White ◽  
Xiaochun Ding ◽  
Johanna C. vanderSpek ◽  
John R. Murphy ◽  
Dagmar Ringe
Keyword(s):  
Diphtheria Toxin ◽  
Metal Ion ◽  
Diphtheria Toxin Repressor

Diphtheria Toxin Repressor: Metal Ion Mediated Control of Transcription

2006 ◽  
Author(s):  
Dagmar Ringe ◽  
Andre White ◽  
Shuyan Chen ◽  
John R Murphy
Keyword(s):  
Diphtheria Toxin ◽  
Metal Ion ◽  
Diphtheria Toxin Repressor

Role of the N-Terminal Helix in the Metal Ion-Induced Activation of the Diphtheria Toxin Repressor DtxR

Biochemistry ◽  
2007 ◽  
Vol 46 (42) ◽  
pp. 11761-11770 ◽  
Author(s):  
J. Alejandro D'Aquino ◽  
Judith R. Lattimer ◽  
Andrew Denninger ◽  
Katharine E. D'Aquino ◽  
Dagmar Ringe
Keyword(s):  
Diphtheria Toxin ◽  
Metal Ion ◽  
Diphtheria Toxin Repressor

scholarly journals Mechanism of metal ion activation of the diphtheria toxin repressor DtxR

2005 ◽  
Vol 102 (51) ◽  
pp. 18408-18413 ◽  
Author(s):  
J. A. D'Aquino ◽  
J. Tetenbaum-Novatt ◽  
A. White ◽  
F. Berkovitch ◽  
D. Ringe
Keyword(s):  
Diphtheria Toxin ◽  
Metal Ion ◽  
Ion Activation ◽  
Diphtheria Toxin Repressor ◽  
Metal Ion Activation

scholarly journals The src Homology 3-Like Domain of the Diphtheria Toxin Repressor (DtxR) Modulates Repressor Activation through Interaction with the Ancillary Metal Ion-Binding Site

2003 ◽  
Vol 185 (7) ◽  
pp. 2251-2258 ◽  
Author(s):  
John F. Love ◽  
Johanna C. vanderSpek ◽  
John R. Murphy
Keyword(s):  
Transition Metal ◽  
Binding Site ◽  
Diphtheria Toxin ◽  
Metal Ion ◽  
Ion Binding ◽  
Metal Ion Binding ◽  
Binding Studies ◽  
Transition Metal Ion ◽  
Diphtheria Toxin Repressor

ABSTRACT The diphtheria toxin repressor (DtxR) is a transition metal ion-activated repressor that acts as a global regulatory element in the control of iron-sensitive genes in Corynebacterium diphtheriae. We recently described (L. Sun, J. C. vanderSpek, and J. R. Murphy, Proc. Natl. Acad. Sci. USA 95:14985-14990, 1998) the isolation and in vivo characterization of a hyperactive mutant of DtxR, DtxR(E175K), that appeared to be constitutively active. We demonstrate here that while DtxR(E175K) remains active in vivo in the presence of 300 μM 2,2′dipyridyl, the purified repressor is, in fact, dependent upon low levels of transition metal ion to transit from the inactive apo form to the active metal ion-bound form of the repressor. Binding studies using 8-anilino-1-naphthalenesulfonic acid suggest that the E175K mutation stabilizes an intermediate of the molten-globule form of the repressor, increasing exposure of hydrophobic residues to solvent. We demonstrate that the hyperactive DtxR(E175K) phenotype is dependent upon an intact ancillary metal ion-binding site (site 1) of the repressor. These observations support the hypothesis that metal ion binding in the ancillary site facilitates the conversion of the inactive apo-repressor to its active, operator-binding conformation. Furthermore, these results support the hypothesis that the C-terminal src homology 3-like domain of DtxR plays an active role in the modulation of repressor activity.

Prolylpeptide Binding by the Prokaryotic SH3-like Domain of the Diphtheria Toxin Repressor:  A Regulatory Switch†,‡

Biochemistry ◽  
2005 ◽  
Vol 44 (1) ◽  
pp. 40-51 ◽  
Author(s):  
Gregory P. Wylie ◽  
Vijayaraghavan Rangachari ◽  
Ewa A. Bienkiewicz ◽  
Vedrana Marin ◽  
Nilakshee Bhattacharya ◽  
...  
Keyword(s):  
Diphtheria Toxin ◽  
Diphtheria Toxin Repressor

scholarly journals Construction and Characterization of Transposon Insertion Mutations in Corynebacterium diphtheriae That Affect Expression of the Diphtheria Toxin Repressor (DtxR)

2002 ◽  
Vol 184 (20) ◽  
pp. 5723-5732 ◽  
Author(s):  
Diana Marra Oram ◽  
Ana Avdalovic ◽  
Randall K. Holmes
Keyword(s):  
Oxidative Stress ◽  
Diphtheria Toxin ◽  
Corynebacterium Diphtheriae ◽  
Insertion Mutant ◽  
Toxin Gene ◽  
Wild Type ◽  
Transposon Insertion ◽  
Diphtheria Toxin Repressor ◽  
Mutant Strains

ABSTRACT Transcription of the bacteriophage-borne diphtheria toxin gene tox is negatively regulated, in response to intracellular Fe2+ concentration, by the chromosomally encoded diphtheria toxin repressor (DtxR). Due to a scarcity of tools, genetic analysis of Corynebacterium diphtheriae has primarily relied on analysis of chemically induced and spontaneously occurring mutants and on the results of experiments with C. diphtheriae genes cloned in Escherichia coli or analyzed in vitro. We modified a Tn5-based mutagenesis technique for use with C. diphtheriae, and we used it to construct the first transposon insertion libraries in the chromosome of this gram-positive pathogen. We isolated two insertions that affected expression of DtxR, one 121 bp upstream of dtxR and the other within an essential region of the dtxR coding sequence, indicating for the first time that dtxR is a dispensable gene in C. diphtheriae. Both mutant strains secrete diphtheria toxin when grown in medium containing sufficient iron to repress secretion of diphtheria toxin by wild-type C. diphtheriae. The upstream insertion mutant still produces DtxR in decreased amounts and regulates siderophore secretion in response to iron in a manner similar to its wild-type parent. The mutant containing the transposon insertion within dtxR does not produce DtxR and overproduces siderophore in the presence of iron. Differences in the ability of the two mutant strains to survive oxidative stress also indicated that the upstream insertion retained slight DtxR activity, whereas the insertion within dtxR abolished DtxR activity. This is the first evidence that DtxR plays a role in protecting the cell from oxidative stress.

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