8KE8

Crystal structure of TetR-type transcriptional factor NalC from P. aeruginosa

Summary for 8KE8

• Entry DOI: 10.2210/pdb8ke8/pdb
• Descriptor: NalC (2 entities in total)
• Functional Keywords: nalc, tetr-type transcriptional factor, multi-drug efflux system, dna binding protein
• Biological source: Pseudomonas aeruginosa PAO1
• Total number of polymer chains: 2
• Total formula weight: 47117.83

Authors

Lee, J.Y.,Jeong, K.H.,Ko, J.H.,Son, S.B. (deposition date: 2023-08-11, release date: 2023-09-20)

Primary citation

Jeong, K.H.,Ko, J.H.,Son, S.B.,Lee, J.Y.
Structural insights into the transcriptional regulator NalC, a key component of the MexAB-OprM efflux pump system, from Pseudomonas aeruginosa.
Biochem.Biophys.Res.Commun., 679:47-51, 2023

PubMed Abstract: Pseudomonas aeruginosa is an opportunistic pathogen with significant public health implications due to its multi-drug resistance (MDR). Among the mechanisms that mediate MDR, the NalC protein, a member of the TetR family of transcriptional regulators, modulates the mexAB-oprM operon, thus facilitating the efflux pump system. The resistance-nodulation-division (RND) family of multidrug efflux pumps plays a crucial role in expelling a broad spectrum of antimicrobial compounds, serving as a key adaptive mechanism. Structural analyses revealed that NalC adopts a modular architecture consisting of distinct domains involved in ligand recognition and transcriptional regulation. The N-terminal domain of NalC contains a DNA-binding helix-turn-helix motif, which interacts with specific DNA sequences in the PA3720-armR operon region. This interaction initiates the transcriptional activation of the efflux pump system. On the other hand, the C-terminal domain of NalC exhibits a highly dynamic structure and is implicated in ligand sensing and signal transduction. Our findings suggest potential binding sites for small molecules that could act as allosteric modulators, thereby providing new avenues for the development of therapeutic strategies targeting MDR Pseudomonas aeruginosa.

PubMed: 37666047
DOI: 10.1016/j.bbrc.2023.08.065

Experimental method

X-RAY DIFFRACTION (2.05 Å)