5DAJ

Crystal structure of NalD, the secondary repressor of MexAB-OprM multidrug efflux pump in Pseudomonas aeruginosa

Summary for 5DAJ

• Entry DOI: 10.2210/pdb5daj/pdb
• Descriptor: NalD (2 entities in total)
• Functional Keywords: repressor, transcriptional regulator, tetr family, transcription regulator
• Biological source: Pseudomonas aeruginosa PAO1
• Total number of polymer chains: 8
• Total formula weight: 198683.92

Authors

Chen, W.Z.,Wang, D.,Huang, S.Q.,Hu, Q.Y.,Liu, X.C.,Gan, J.H.,Chen, H. (deposition date: 2015-08-20, release date: 2016-04-20, Last modification date: 2024-10-16)

Primary citation

Chen, W.Z.,Wang, D.,Zhou, W.,Sang, H.,Liu, X.C.,Ge, Z.,Zhang, J.,Lan, L.,Yang, C.G.,Chen, H.
Novobiocin binding to NalD induces the expression of the MexAB-OprM pump in Pseudomonas aeruginosa
Mol.Microbiol., 100:749-758, 2016

PubMed Abstract: NalD was reported to be the secondary repressor of the MexAB-OprM multidrug efflux pump, the major system contributing to intrinsic multidrug resistance in Pseudomonas aeruginosa. Here, we show that novobiocin binds directly to NalD, which leads NalD to dissociate from the DNA promoter, and thus de-represses the expression of the MexAB-OprM pump. In addition, we have solved the crystal structure of NalD at a resolution of 2.90 Å. The structural alignment of NalD to its homologue TtgR reveals that the residues N129 and H167 in NalD are involved in its novobiocin-binding ability. We have confirmed the function of these two amino acids by EMSA and plate assay. The results presented here highlight the importance and diversity of regulatory mechanism in bacterial antibiotic resistance, and provide further insight for novel antimicrobial development.

PubMed: 26844397
DOI: 10.1111/mmi.13346

Experimental method

X-RAY DIFFRACTION (2.65 Å)