3V6G

Crystal Structure of Transcriptional Regulator

Summary for 3V6G

• Entry DOI: 10.2210/pdb3v6g/pdb
• Related: 3V78
• Descriptor: PROBABLE TRANSCRIPTIONAL REGULATORY PROTEIN (PROBABLY DEOR-FAMILY) (2 entities in total)
• Functional Keywords: helix-turn-helix dna binding domain, transcription
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 2
• Total formula weight: 45633.02

Authors

Do, S.V.,Bolla, J.R.,Chen, X.,Yu, E.W. (deposition date: 2011-12-19, release date: 2012-08-08, Last modification date: 2024-02-28)

Primary citation

Bolla, J.R.,Do, S.V.,Long, F.,Dai, L.,Su, C.C.,Lei, H.T.,Chen, X.,Gerkey, J.E.,Murphy, D.C.,Rajashankar, K.R.,Zhang, Q.,Yu, E.W.
Structural and functional analysis of the transcriptional regulator Rv3066 of Mycobacterium tuberculosis.
Nucleic Acids Res., 40:9340-9355, 2012

PubMed Abstract: The Mmr multidrug efflux pump recognizes and actively extrudes a broad range of antimicrobial agents, and promotes the intrinsic resistance to these antimicrobials in Mycobacterium tuberculosis. The expression of Mmr is controlled by the TetR-like transcriptional regulator Rv3066, whose open reading frame is located downstream of the mmr operon. To understand the structural basis of Rv3066 regulation, we have determined the crystal structures of Rv3066, both in the absence and presence of bound ethidium, revealing an asymmetric homodimeric two-domain molecule with an entirely helical architecture. The structures underscore the flexibility and plasticity of the regulator essential for multidrug recognition. Comparison of the apo-Rv3066 and Rv3066-ethidium crystal structures suggests that the conformational changes leading to drug-mediated derepression is primarily due to a rigid body rotational motion within the dimer interface of the regulator. The Rv3066 regulator creates a multidrug-binding pocket, which contains five aromatic residues. The bound ethidium is found buried within the multidrug-binding site, where extensive aromatic stacking interactions seemingly govern the binding. In vitro studies reveal that the dimeric Rv3066 regulator binds to a 14-bp palindromic inverted repeat sequence in the nanomolar range. These findings provide new insight into the mechanisms of ligand binding and Rv3066 regulation.

PubMed: 22821564
DOI: 10.1093/nar/gks677

Experimental method

X-RAY DIFFRACTION (1.821 Å)