3U6K

Ef-tu (escherichia coli) in complex with nvp-ldk733


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.45 Å
  • R-Value Free: 0.298 
  • R-Value Work: 0.224 
  • R-Value Observed: 0.228 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.0 of the entry. See complete history


Literature

Antibacterial optimization of 4-aminothiazolyl analogues of the natural product GE2270 A: identification of the cycloalkylcarboxylic acids.

LaMarche, M.J.Leeds, J.A.Amaral, K.Brewer, J.T.Bushell, S.M.Dewhurst, J.M.Dzink-Fox, J.Gangl, E.Goldovitz, J.Jain, A.Mullin, S.Neckermann, G.Osborne, C.Palestrant, D.Patane, M.A.Rann, E.M.Sachdeva, M.Shao, J.Tiamfook, S.Whitehead, L.Yu, D.

(2011) J Med Chem 54: 8099-8109

  • DOI: https://doi.org/10.1021/jm200938f
  • Primary Citation of Related Structures:  
    3U6B, 3U6K

  • PubMed Abstract: 

    4-Aminothiazolyl analogues of the antibiotic natural product GE2270 A (1) were designed, synthesized, and optimized for their activity against Gram positive bacterial infections. Optimization efforts focused on improving the physicochemical properties (e.g., aqueous solubility and chemical stability) of the 4-aminothiazolyl natural product template while improving the in vitro and in vivo antibacterial activity. Structure-activity relationships were defined, and the solubility and efficacy profiles were improved over those of previous analogues and 1. These studies identified novel, potent, soluble, and efficacious elongation factor-Tu inhibitors, which bear cycloalkylcarboxylic acid side chains, and culminated in the selection of development candidates amide 48 and urethane 58.


  • Organizational Affiliation

    Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Cambridge, Massachusetts 02139, United States. matthew.lamarche@novartis.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Elongation factor Tu 1
A, B
394Escherichia coli K-12Mutation(s): 0 
Gene Names: tufAb3339JW3301
UniProt
Find proteins for P0CE47 (Escherichia coli (strain K12))
Explore P0CE47 
Go to UniProtKB:  P0CE47
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0CE47
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Thiocillin GE2270 analogue NVP-LDK733
C, D
12Planobispora roseaMutation(s): 0 
UniProt
Find proteins for Q7M0J8 (Planobispora rosea)
Explore Q7M0J8 
Go to UniProtKB:  Q7M0J8
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ7M0J8
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  6 Unique
IDChains TypeFormula2D DiagramParent
BB6
Query on BB6
C, D
PEPTIDE LINKINGC4 H7 N O2 SCYS
BB7
Query on BB7
C, D
PEPTIDE LINKINGC5 H9 N O3 SCYS
BB8
Query on BB8
C, D
L-PEPTIDE LINKINGC9 H11 N O3PHE
BB9
Query on BB9
C, D
PEPTIDE LINKINGC3 H5 N O2 SCYS
MEN
Query on MEN
C, D
L-PEPTIDE LINKINGC5 H10 N2 O3ASN
MH6
Query on MH6
C, D
PEPTIDE LINKINGC3 H5 N O3SER
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.45 Å
  • R-Value Free: 0.298 
  • R-Value Work: 0.224 
  • R-Value Observed: 0.228 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 80.372α = 90
b = 82.216β = 90
c = 129.9γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
PHASERphasing
CNXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-02-08
    Type: Initial release
  • Version 1.1: 2012-04-18
    Changes: Structure summary
  • Version 1.2: 2012-12-12
    Changes: Other
  • Version 2.0: 2023-11-15
    Changes: Atomic model, Data collection, Database references, Derived calculations, Polymer sequence, Structure summary