PDBsum entry: 1exj

Transcription/DNA

PDB id: 1exj

Contents

Protein chain

275 a.a. *

DNA/RNA

Ligands

P4P

Metals

_NA

_ZN

Waters ×5

* Residue conservation analysis

PDB id:

1exj

Name:

Transcription/DNA

Title:

Crystal structure of transcription activator bmrr, from b. Subtilis, bound to 21 base pair bmr operator and tpp

Structure:

DNA (5'- d( Ap Cp Cp Cp Tp Cp Cp Cp Cp Tp Tp Ap Gp Gp Gp Gp Ap Gp Gp Gp T)-3'). Chain: m. Engineered: yes. Multidrug-efflux transporter regulator. Chain: a. Synonym: transcription activator bmrr. Engineered: yes

Source:

Synthetic: yes. Bacillus subtilis. Organism_taxid: 1423. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Tetramer (from PDB file)

Resolution:

3.00Å R-factor: 0.240 R-free: 0.315

Authors:

E.E.Zheleznova-Heldwein,R.G.Brennan

Key ref:

E.E.Heldwein and R.G.Brennan (2001). Crystal structure of the transcription activator BmrR bound to DNA and a drug. Nature, 409, 378-382. PubMed id: 11201751 DOI: 10.1038/35053138

Date:

02-May-00 Release date: 24-Jan-01

Protein chain

P39075  (BMRR_BACSU) -  Multidrug-efflux transporter 1 regulator

Seq: 278 a.a.

Struc: 275 a.a.

 Gene Ontology (GO) functional annotation 

• Biological process: regulation of transcription (3 terms)
• Biochemical function: nucleotide binding (3 terms)

DOI no: 10.1038/35053138

Nature 409:378-382 (2001)

PubMed id: 11201751

Crystal structure of the transcription activator BmrR bound to DNA and a drug.

E.E.Heldwein, R.G.Brennan.

ABSTRACT

The efflux of chemically diverse drugs by multidrug transporters that span the membrane is one mechanism of multidrug resistance in bacteria. The concentrations of many of these transporters are controlled by transcription regulators, such as BmrR in Bacillus subtilis, EmrR in Escherichia coli and QacR in Staphylococcus aureus. These proteins promote transporter gene expression when they bind toxic compounds. BmrR activates transcription of the multidrug transporter gene, bmr, in response to cellular invasion by certain lipophilic cationic compounds (drugs). BmrR belongs to the MerR family, which regulates response to stress such as exposure to toxic compounds or oxygen radicals in bacteria. MerR proteins have homologous amino-terminal DNA-binding domains but different carboxy-terminal domains, which enable them to bind specific 'coactivator' molecules. When bound to coactivator, MerR proteins upregulate transcription by reconfiguring the 19-base-pair spacer found between the -35 and -10 promoter elements to allow productive interaction with RNA polymerase. Here we report the 3.0 A resolution structure of BmrR in complex with the drug tetraphenylphosphonium (TPP) and a 22-base-pair oligodeoxynucleotide encompassing the bmr promoter. The structure reveals an unexpected mechanism for transcription activation that involves localized base-pair breaking, and base sliding and realignment of the -35 and -10 operator elements.

Selected figure(s)

Figure 1.
Figure 1: Crystal structure of the BmrR -drug -DNA complex. a, BmrR monomer. The DNA-binding domain, -helical linker and drug-binding domain are shown in yellow, red and green, respectively. b, BmrR dimer bound to DNA. One monomer is coloured as in a, whereas the other monomer is shown in cyan. DNA and TPP/TPSb are represented as balls and sticks (carbon, black; nitrogen, blue; oxygen, red; and phosphorus/antimony, green). c, Dimerization interface between the drug-binding domain of a BmrR monomer (green) and the DNA-binding domain of its dimeric mate (cyan). The TPP/TPSb molecule and selected drug-binding residues are are represented as ball and sticks.

Figure 2.
Figure 2: BmrR -DNA interactions. a, BmrR -DNA half-site interface. Atoms are represented as sticks (carbon, black; nitrogen, blue; oxygen, red; phosphorus, yellow). Hydrogen bonds are represented as yellow dashed lines. b, Representation of BmrR -DNA contacts. DNA is shown as a cylindrical projection where bases are depicted as rectangular boxes, deoxyribose rings as pentagons, and phosphates as circles. Hydrogen bonds are represented as blue, and van der Waals interactions as green arrows. Solid and dashed lines represent contacts from side chains and backbone amides, respectively. Side chains that contact bases in the major or minor grooves are labelled with 'M' and 'm', respectively.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2001, 409, 378-382) copyright 2001.

Figures were selected by an automated process.