8WRF

Crystal structure of MexL

Summary for 8WRF

• Entry DOI: 10.2210/pdb8wrf/pdb
• Descriptor: Probable transcriptional regulator (1 entity in total)
• Functional Keywords: tetr family, transcription
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 2
• Total formula weight: 44382.90

Authors

Wei, Y.,Wu, Z.K. (deposition date: 2023-10-14, release date: 2025-03-05, Last modification date: 2025-03-12)

Primary citation

Yu, Z.,Wu, Z.,Liu, D.,Liu, H.,Zhang, Y.,Zheng, Y.,Huang, Y.,Liao, S.,Wei, Y.,Huang, W.,Zhang, Z.,Liu, X.,Yu, H.,Wang, D.,Li, L.,Long, F.,Ma, L.Z.
Dual-function regulator MexL as a target to control phenazines production and pathogenesis of Pseudomonas aeruginosa.
Nat Commun, 16:2000-2000, 2025

PubMed Abstract: Antibiotic resistance or tolerance of pathogens has become one of the global public crises. Finding new drug targets may open up a way of infection control. Phenazine pyocyanin (PYO) is an important virulence factor produced by the pathogen Pseudomonas aeruginosa. Here we show that a multidrug efflux pump repressor, MexL, acts as a transcriptional activator to enhance phenazines production via binding with a conserved DNA motif within the promoters of phenazines biosynthesis genes. Moreover, PYO functions as a self-regulating ligand of MexL for restricting its own production and the mexL knockout attenuates the virulence and antibiotics tolerance of P. aeruginosa. Based on the structure of MexL we resolve, we find two antimicrobials that can interact with MexL to reduce the PYO production and virulence of P. aeruginosa. Our in vivo studies suggest that the antimicrobials combination by using MexL-antagonists to reduce bacterial virulence and enhance the efficacy of common antibiotics can be an effective way to combat P. aeruginosa infection.

PubMed: 40011517
DOI: 10.1038/s41467-025-57294-8

Experimental method

X-RAY DIFFRACTION (3 Å)