4ZIJ

Crystal structure of E.Coli DsbA in complex with 2-(4-iodophenylsulfonamido) benzoic acid


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.78 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.173 
  • R-Value Observed: 0.176 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Determination of ligand binding modes in weak protein-ligand complexes using sparse NMR data.

Mohanty, B.Williams, M.L.Doak, B.C.Vazirani, M.Ilyichova, O.Wang, G.Bermel, W.Simpson, J.S.Chalmers, D.K.King, G.F.Mobli, M.Scanlon, M.J.

(2016) J Biomol NMR 66: 195-208

  • DOI: https://doi.org/10.1007/s10858-016-0067-4
  • Primary Citation of Related Structures:  
    2NDO, 4ZIJ

  • PubMed Abstract: 

    We describe a general approach to determine the binding pose of small molecules in weakly bound protein-ligand complexes by deriving distance constraints between the ligand and methyl groups from all methyl-containing residues of the protein. We demonstrate that using a single sample, which can be prepared without the use of expensive precursors, it is possible to generate high-resolution data rapidly and obtain the resonance assignments of Ile, Leu, Val, Ala and Thr methyl groups using triple resonance scalar correlation data. The same sample may be used to obtain Met ε CH 3 assignments using NOESY-based methods, although the superior sensitivity of NOESY using [U- 13 C, 15 N]-labeled protein makes the use of this second sample more efficient. We describe a structural model for a weakly binding ligand bound to its target protein, DsbA, derived from intermolecular methyl-to-ligand nuclear Overhauser enhancements, and demonstrate that the ability to assign all methyl resonances in the spectrum is essential to derive an accurate model of the structure. Once the methyl assignments have been obtained, this approach provides a rapid means to generate structural models for weakly bound protein-ligand complexes. Such weak complexes are often found at the beginning of programs of fragment based drug design and can be challenging to characterize using X-ray crystallography.


  • Organizational Affiliation

    Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Thiol:disulfide interchange protein DsbA
A, B
188Escherichia coli K-12Mutation(s): 0 
Gene Names: dsbAdsfppfAb3860JW3832
UniProt
Find proteins for P0AEG4 (Escherichia coli (strain K12))
Explore P0AEG4 
Go to UniProtKB:  P0AEG4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0AEG4
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SFQ
Query on SFQ

Download Ideal Coordinates CCD File 
C [auth A]2-{[(4-iodophenyl)sulfonyl]amino}benzoic acid
C13 H10 I N O4 S
PLJIQKJMJAHNRG-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
D [auth B]1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
SFQ Binding MOAD:  4ZIJ Kd: 5.65e+5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.78 Å
  • R-Value Free: 0.217 
  • R-Value Work: 0.173 
  • R-Value Observed: 0.176 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 123.965α = 90
b = 46.982β = 96.2
c = 62.288γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing
Blu-Icedata collection

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Health and Medical Research Council (NHMRC, Australia)Australia1009785
Australian Research Council (ARC)AustraliaCE0562063
Australian Research Council (ARC)AustraliaFT110100925

Revision History  (Full details and data files)

  • Version 1.0: 2016-05-11
    Type: Initial release
  • Version 1.1: 2016-11-09
    Changes: Database references
  • Version 1.2: 2016-12-07
    Changes: Database references
  • Version 1.3: 2017-09-06
    Changes: Author supporting evidence, Data collection, Database references
  • Version 1.4: 2020-01-01
    Changes: Author supporting evidence
  • Version 1.5: 2023-09-27
    Changes: Data collection, Database references, Refinement description