6IDE

Crystal structure of the Vibrio cholera VqmA-Ligand-DNA complex provides molecular mechanisms for drug design

Summary for 6IDE

• Entry DOI: 10.2210/pdb6ide/pdb
• Descriptor: Transcriptional regulator LuxR family, DNA (5'-D(*AP*GP*GP*GP*GP*GP*GP*AP*AP*AP*TP*CP*CP*CP*CP*CP*CP*T)-3'), DNA (5'-D(*AP*GP*GP*GP*GP*GP*GP*AP*TP*TP*TP*CP*CP*CP*CP*CP*CP*T)-3'), ... (5 entities in total)
• Functional Keywords: vibrio cholera, quorum sensing, transcription regulator, transcription-dna complex, transcription/dna
• Biological source: Vibrio cholerae; More
• Total number of polymer chains: 4
• Total formula weight: 69019.68

Authors

Wu, H.,Li, M.J.,Guo, H.J.,Zhou, H.,Li, B.,Xu, Q.,Xu, C.Y.,Yu, F.,He, J.H. (deposition date: 2018-09-09, release date: 2019-01-16, Last modification date: 2024-03-27)

Primary citation

Wu, H.,Li, M.,Guo, H.,Zhou, H.,Li, B.,Xu, Q.,Xu, C.,Yu, F.,He, J.
Crystal structure of theVibrio choleraeVqmA-ligand-DNA complex provides insight into ligand-binding mechanisms relevant for drug design.
J. Biol. Chem., 294:2580-2592, 2019

PubMed Abstract: VqmA is a highly conserved transcriptional regulator of the quorum-sensing system of , a major human pathogen that continues to imperil human health. VqmA represses biofilm formation and plays an important role in pathogenicity in the human host. Although VqmA's biological function is well understood, the molecular mechanisms by which its specific ligand (and effector), 3,5-dimethylpyrazine-2-ol (DPO), controls transcription of the target gene, , remain obscure. To elucidate the molecular mechanism of DPO binding, we used structural analyses and biochemical assays to study the VqmA-DPO-DNA complex. These analyses revealed that VqmA contains an N-terminal homodimer domain (PAS) and a C-terminal DNA-binding domain (DBD). We observed that VqmA directly binds to a DPO molecule via a compact hydrophobic pocket, consisting of a six-stranded antiparallel β-sheet and several α-helices. We also found that the VqmA dimer interacts with the quasi-palindromic sequence of the promoter through its DBD. The results of the biochemical studies indicated that a water atom and VqmA residues Phe-67 and Lys-101 play a key role in effector recognition, which is also assisted by Tyr-36 and Phe-99. This is the first molecular level view of the VqmA dimer bound to DPO and DNA. The structure-function analyses presented here improve our understanding of the complex mechanisms in the transcriptional regulation of VqmA in spp. and may inform the design of drugs to manage infections.

PubMed: 30610119
DOI: 10.1074/jbc.RA118.006082

Experimental method

X-RAY DIFFRACTION (2.51 Å)