3F8B

Crystal structure of the multidrug binding transcriptional regulator LmrR in drug free state

Summary for 3F8B

• Entry DOI: 10.2210/pdb3f8b/pdb
• Related: 3F8C 3F8F
• Descriptor: Transcriptional regulator, PadR-like family (2 entities in total)
• Functional Keywords: winged helix turn helix, transcription regulator
• Biological source: Lactococcus lactis subsp. cremoris
• Total number of polymer chains: 2
• Total formula weight: 26956.74

Authors

Madoori, P.K.,Agustiandari, H.,Driessen, A.J.M.,Thunnissen, A.-M.W.H. (deposition date: 2008-11-12, release date: 2008-12-30, Last modification date: 2023-11-01)

Primary citation

Madoori, P.K.,Agustiandari, H.,Driessen, A.J.,Thunnissen, A.M.
Structure of the transcriptional regulator LmrR and its mechanism of multidrug recognition.
Embo J., 28:156-166, 2009

PubMed Abstract: LmrR is a PadR-related transcriptional repressor that regulates the production of LmrCD, a major multidrug ABC transporter in Lactococcus lactis. Transcriptional regulation is presumed to follow a drug-sensitive induction mechanism involving the direct binding of transporter ligands to LmrR. Here, we present crystal structures of LmrR in an apo state and in two drug-bound states complexed with Hoechst 33342 and daunomycin. LmrR shows a common topology containing a typical beta-winged helix-turn-helix domain with an additional C-terminal helix involved in dimerization. Its dimeric organization is highly unusual with a flat-shaped hydrophobic pore at the dimer centre serving as a multidrug-binding site. The drugs bind in a similar manner with their aromatic rings sandwiched in between the indole groups of two dimer-related tryptophan residues. Multidrug recognition is facilitated by conformational plasticity and the absence of drug-specific hydrogen bonds. Combined analyses using site-directed mutagenesis, fluorescence-based drug binding and protein-DNA gel shift assays reveal an allosteric coupling between the multidrug- and DNA-binding sites of LmrR that most likely has a function in the induction mechanism.

PubMed: 19096365
DOI: 10.1038/emboj.2008.263

Experimental method

X-RAY DIFFRACTION (2 Å)