6IDE

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.51 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.193 

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This is version 1.2 of the entry. See complete history


Literature

Crystal structure of theVibrio choleraeVqmA-ligand-DNA complex provides insight into ligand-binding mechanisms relevant for drug design.

Wu, H.Li, M.Guo, H.Zhou, H.Li, B.Xu, Q.Xu, C.Yu, F.He, J.

(2019) J Biol Chem 294: 2580-2592

  • DOI: https://doi.org/10.1074/jbc.RA118.006082
  • Primary Citation of Related Structures:  
    6IDE

  • PubMed Abstract: 

    VqmA is a highly conserved transcriptional regulator of the quorum-sensing system of Vibrio cholerae , a major human pathogen that continues to imperil human health. VqmA represses biofilm formation and plays an important role in V. cholerae 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, vqmR , remain obscure. To elucidate the molecular mechanism of DPO binding, we used structural analyses and biochemical assays to study the V. cholerae 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 vqmR 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 Vibrio spp. and may inform the design of drugs to manage V. cholerae infections.


  • Organizational Affiliation

    From the Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 and.


Macromolecules

Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Transcriptional regulator LuxR family
A, B
256Vibrio choleraeMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains LengthOrganismImage
DNA (5'-D(*AP*GP*GP*GP*GP*GP*GP*AP*AP*AP*TP*CP*CP*CP*CP*CP*CP*T)-3')18Vibrio cholerae
Sequence Annotations
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  • Reference Sequence

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Entity ID: 3
MoleculeChains LengthOrganismImage
DNA (5'-D(*AP*GP*GP*GP*GP*GP*GP*AP*TP*TP*TP*CP*CP*CP*CP*CP*CP*T)-3')18Vibrio cholerae
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.51 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.193 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 52.78α = 90
b = 108.98β = 90
c = 214.32γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
Aimlessdata scaling
CRANK2phasing
PDB_EXTRACTdata extraction
xia2data reduction

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Natural Science Foundation of ChinaChina31570740
National Natural Science Foundation of ChinaChina81330076

Revision History  (Full details and data files)

  • Version 1.0: 2019-01-16
    Type: Initial release
  • Version 1.1: 2019-03-06
    Changes: Data collection, Database references
  • Version 1.2: 2024-03-27
    Changes: Data collection, Database references