SMART: HTH_DTXR domain annotation

HTH_DTXR Helix-turn-helix diphteria tox regulatory element

SMART accession number:	SM00529
Description:	iron dependent repressor
Interpro abstract (IPR022689):	The diphtheria toxin repressor protein (DTXR) is a member of this group [(PUBMED:7568230)]. In Corynebacterium diphtheriae where it has been studied in some detail this protein acts as an iron-binding repressor of dipheteria toxin gene expression and may serve as a global regulator of gene expression. The N terminus may be involved in iron binding and may associate with the Tox operator. Binding of DTXR to Tox operator requires a divalent metal ion such as cobalt, ferric, manganese and nickel whereas zinc shows weak activation [(PUBMED:7743135)].
GO process:	regulation of transcription, DNA-dependent (GO:0006355)
GO function:	transition metal ion binding (GO:0046914), sequence-specific DNA binding transcription factor activity (GO:0003700)
Family alignment:	View or

There are 994 HTH_DTXR domains in 994 proteins in SMART's nrdb database.

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Evolution (species in which this domain is found)
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Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Qiu X, Verlinde CL, Zhang S, Schmitt MP, Holmes RK, Hol WG
- Three-dimensional structure of the diphtheria toxin repressor in complex with divalent cation co-repressors.
- Structure. 1995; 3: 87-100
- Display abstract
- BACKGROUND: When Corynebacterium diphtheriae encounters an environment with a low concentration of iron ions, it initiates the synthesis of several virulence factors, including diphtheria toxin. The diphtheria toxin repressor (DtxR) plays a key role in this iron-dependent, global regulatory system and is the prototype for a new family of iron-dependent repressor proteins in Gram-positive bacteria. This study aimed to increase understanding of the general regulatory principles of cation binding to DtxR. RESULTS: The crystal structure of dimeric DtxR holo-repressor in complex with different transition metals shows that each subunit comprises an amino-terminal DNA-binding domain, an interface domain (which contains two metal-binding sites) and a third, very flexible carboxy-terminal domain. Each DNA-binding domain contains a helix-turn-helix motif and has a topology which is very similar to catabolite gene activator protein (CAP). Molecular modeling suggests that bound DNA adopts a bent conformation with helices alpha 3 of DtxR interacting with the major grooves. The two metal-binding sites lie approximately 10 A apart. Binding site 2 is positioned at a potential hinge region between the DNA-binding and interface domains. Residues 98-108 appear to be crucial for the functioning of the repressor; these provide four of the ligands of the two metal-binding sites and three residues at the other side of the helix which are at the heart of the dimer interface. CONCLUSIONS: The crystal structure of the DtxR holorepressor suggests that the divalent cation co-repressor controls motions of the DNA-binding domain. In this way the metal co-repressor governs the distance between operator recognition elements in the two subunits and, consequently, DNA recognition.
- Schiering N, Tao X, Zeng H, Murphy JR, Petsko GA, Ringe D
- Structures of the apo- and the metal ion-activated forms of the diphtheria tox repressor from Corynebacterium diphtheriae.
- Proc Natl Acad Sci U S A. 1995; 92: 9843-50
- Display abstract
- The diphtheria tox repressor (DtxR) of Corynebacterium diphtheriae plays a critical role in the regulation of diphtheria toxin expression and the control of other iron-sensitive genes. The crystal structures of apo-DtxR and of the metal ion-activated form of the repressor have been solved and used to identify motifs involved in DNA and metal ion binding. Residues involved in binding of the activated repressor to the diphtheria tox operator, glutamine 43, arginine 47, and arginine 50, were located and confirmed by site-directed mutagenesis. Previous biochemical and genetic data can be explained in terms of these structures. Conformational differences between apo- and Ni-DtxR are discussed with regard to the mechanism of action of this repressor.
Metabolism (metabolic pathways involving proteins which contain this domain)

Structure (3D structures containing this domain)

3D Structures of HTH_DTXR domains in PDB

PDB code	Main view	Title
1b1b		Iron dependent regulator
1bi0		Structure of apo-and holo-diphtheria toxin repressor
1bi1		Structure of apo-and holo-diphtheria toxin repressor
1bi2		Structure of apo-and holo-diphtheria toxin repressor
1bi3		Structure of apo-and holo-diphtheria toxin repressor
1c0w		Crystal structure of the cobalt-activated diphtheria toxin repressor-dna complex reveals a metal binding sh-like domain
1ddn		Diphtheria tox repressor (c102d mutant)/tox dna operator complex
1dpr		Structures of the apo-and metal ion activated forms of the diphtheria tox repressor from corynebacterium diphtheriae
1f5t		Diphtheria tox repressor (c102d mutant) complexed with nickel and dtxr consensus binding sequence
1fwz		Glu20ala dtxr
1fx7		Crystal structure of the iron-dependent regulator (ider) from mycobacterium tuberculosis
1g3s		Cys102ser dtxr
1g3t		Cys102ser dtxr
1g3w		Cd-cys102ser dtxr
1g3y		Arg80ala dtxr
1on1		Bacillus subtilis manganese transport regulator (mntr) bound to manganese, ab conformation.
1on2		Bacillus subtilis manganese transport regulator (mntr), d8m mutant, bound to manganese
1p92		Crystal structure of (h79a)dtxr
1u8r		Crystal structure of an ider-dna complex reveals a conformational change in activated ider for base-specific interactions
1xcv		Crystal structure of (h79ac102d)dtxr complexed with nickel(ii)
2dtr		Structure of diphtheria toxin repressor
2ev0		Bacillus subtilis manganese transport regulator (mntr) bound to cadmium
2ev5		Bacillus subtilis manganese transport regulator (mntr) bound to calcium
2ev6		Bacillus subtilis manganese transport regulator (mntr) bound to zinc
2f5c		Bacillus subtilis manganese transport regulator (mntr) bound to manganese, hexagonal crystal form
2f5d		Bacillus subtilis manganese transport regulator (mntr) bound to manganese, ac conformation, ph 6.5
2f5e		Bacillus subtilis manganese transport regulator (mntr) bound to manganese, ab conformation, ph 6.5
2f5f		Bacillus subtilis manganese transport regulator (mntr) bound to manganese, ac conformation, ph 8.5
2h09		Crystal structure of diphtheria toxin repressor like protein from e. coli
2hyf		The structure of apo-mntr from bacillus subtilis, selenomethionine derivative
2hyg		The structure of apo-mntr from bacillus subtilis, native form
2isy		Crystal structure of the nickel-activated two-domain iron- dependent regulator (ider)
2isz		Crystal structure of a two-domain ider-dna complex crystal form i
2it0		Crystal structure of a two-domain ider-dna complex crystal form ii
2qq9		Crystal structure of dtxr(d6a c102d) complexed with nickel(ii)
2qqa		Crystal structure of dtxr(e9a c102d) complexed with nickel(ii)
2qqb		Crystal structure of dtxr(m10a c102d) complexed with nickel(ii)
2tdx		Diphtheria tox repressor (c102d mutant) complexed with nickel
3glx		Crystal structure analysis of the dtxr(e175k) complexed with ni(ii)
3hrs		Crystal structure of the manganese-activated repressor scar: apo form
3hrt		Crystal structure of scar with bound cd2+
3hru		Crystal structure of scar with bound zn2+

Links (links to other resources describing this domain)
PFAM Fe_dep_repress
INTERPRO IPR022689