PDBsum entry: 1c0w

Gene regulation/DNA

PDB id: 1c0w

Contents

Protein chains

173 a.a. *

219 a.a. *

DNA/RNA

Metals

_CO ×8

* Residue conservation analysis

PDB id:

1c0w

Name:

Gene regulation/DNA

Title:

Crystal structure of the cobalt-activated diphtheria toxin repressor-DNA complex reveals a metal binding sh-like domain

Structure:

DNA (5'- d(p Ap Tp Tp Ap Gp Gp Tp Tp Ap Gp Cp Cp Tp Ap Cp Cp Cp Tp A p Ap T)-3'). Chain: e. Engineered: yes. DNA (5'- d(p Ap Tp Tp Ap Gp Gp Tp Tp Ap Gp Gp Cp Tp Ap Cp Cp Cp Tp A p Ap T)-3'). Chain: f.

Source:

Synthetic: yes. Corynebacterium diphtheriae. Organism_taxid: 1717. Gene: dtxr. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dodecamer (from PQS)

Resolution:

3.20Å R-factor: 0.249 R-free: 0.279

Authors:

E.Pohl,R.K.Holmes,W.G.Hol

Key ref:

E.Pohl et al. (1999). Crystal structure of a cobalt-activated diphtheria toxin repressor-DNA complex reveals a metal-binding SH3-like domain. J Mol Biol, 292, 653-667. PubMed id: 10497029 DOI: 10.1006/jmbi.1999.3073

Date:

22-Jul-99 Release date: 22-Jul-00

Protein chains

P33120  (DTXR_CORDI) -  Diphtheria toxin repressor

Seq: 226 a.a.

Struc: 173 a.a.*

Protein chain

P33120  (DTXR_CORDI) -  Diphtheria toxin repressor

Seq: 226 a.a.

Struc: 219 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 

• Cellular component: cytoplasm (1 term)
• Biological process: regulation of transcription (3 terms)
• Biochemical function: DNA binding (3 terms)

DOI no: 10.1006/jmbi.1999.3073

J Mol Biol 292:653-667 (1999)

PubMed id: 10497029

Crystal structure of a cobalt-activated diphtheria toxin repressor-DNA complex reveals a metal-binding SH3-like domain.

E.Pohl, R.K.Holmes, W.G.Hol.

ABSTRACT

The diphtheria toxin repressor (DtxR) is the prototype of a family of iron-dependent regulator (IdeR) proteins, which are activated by divalent iron and bind DNA to prevent the transcription of downstream genes. In Corynebacterium diphtheriae, DtxR regulates not only the expression of diphtheria toxin encoded by a corynebacteriophage, but also of components of the siderophore-mediated iron-transport system. Here we report the crystal structure of wild-type DtxR, a 226 residue three-domain dimeric protein, activated by cobalt and bound to a 21 bp DNA duplex based on the consensus operator sequence. Two DtxR dimers surround the DNA duplex which is distorted compared to canonical B -DNA. The SH3-like third domain interacts with the metal at site 1 via the side-chains of Glu170 and Gln173, revealing for the first time a metal-binding function for this class of domains. The SH3-like domain is also in contact with the DNA-binding first domain and with the second, or dimerization, domain. The DNA-binding helices in the first domain are shifted by 3 to 5 A when compared to the apo-repressor, and fit into the major groove of the duplex bound. These shifts are due to a hinge-binding motion of the DNA-binding domain with respect to the dimerization domains of DtxR. The third domain might play a role in regulating this hinge motion.

Selected figure(s)

Figure 3.
Figure 3. Stereoview of the unbiased sA-weighted Fo - Fc electron density contoured at 1.0 s showing the density around metal site 1. (a) Monomer 1; (b) monomer 3. The densities are virtually identical with those observed for the SH3-like domains near monomers 2 and 4, after including the DNA oligonucleotide and the metals in the model for the calculation of Fc.

Figure 6.
Figure 6. Interactions of the SH3-like third domain with the first two domains. (a) Surface representation of parts of domains 1 and 2 of monomer 1 showing interactions with the SH3-like third domain in the Co-wtDtxR-DNA complex. (b) The wedge region of the SH3-like domain of DtxR (residues 165-185). Left: Structure of the wedge region (red). Right: Interactions of the wedge region with the DNA-binding domain (dark blue) and dimerization domain (light blue) at metal site 1. This view is rotated approximately 90 ° with respect to the view at the left. The sphere represents the metal bound at site 1.

The above figures are reprinted by permission from Elsevier: J Mol Biol (1999, 292, 653-667) copyright 1999.

Figures were selected by the author.