4G5G

ef-tu (Escherichia coli) complexed with nvp-ldu796

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.258 
  • R-Value Work: 0.212 

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This is version 3.0 of the entry. See complete history. 


Literature

Antibiotic optimization and chemical structure stabilization of thiomuracin A.

LaMarche, M.J., Leeds, J.A., Dzink-Fox, J., Gangl, E., Krastel, P., Neckermann, G., Palestrant, D., Patane, M.A., Rann, E.M., Tiamfook, S., Yu, D.

(2012) J Med Chem 55: 6934-6941

  • DOI: https://doi.org/10.1021/jm300783c
  • Primary Citation of Related Structures:  
    4G5G

  • PubMed Abstract: 

    Synthetic studies of the antimicrobial secondary metabolite thiomuracin A (1) were initiated to improve chemical stability and physicochemical properties. Functional group modifications of 1 included removing the C2-C7 side chain, derivatizing the C84 epoxide region, and altering the C44 hydroxyphenylalanine motif. The resulting derivatives simplified and stabilized the chemical structure and were evaluated for antibacterial activity relative to 1. The simplified structure and improved organic solubility of the derivatives facilitated isolation yields from fermentation broths and simplified the procedures involved for the process. These advancements increased material supply for continued medicinal chemistry optimization and culminated in the identification of 2, a structurally simplified and chemically stable analogue of 1 which retained potent antibiotic activity.

    • 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 1394Escherichia coli K-12Mutation(s): 0 
Gene Names: tufA, b3339, JW3301
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
thiomuracin A derivativeB [auth I]13synthetic constructMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  5 Unique
IDChains TypeFormula2D DiagramParent
05N
Query on 05N		B [auth I]L-PEPTIDE LINKINGC6 H11 N O3PRO
BB6
Query on BB6		B [auth I]PEPTIDE LINKINGC4 H7 N O2 SCYS
BB9
Query on BB9		B [auth I]PEPTIDE LINKINGC3 H5 N O2 SCYS
H14
Query on H14		B [auth I]L-PEPTIDE LINKINGC9 H11 N O3PHE
MH6
Query on MH6		B [auth I]PEPTIDE LINKINGC3 H5 N O3SER
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.258 
  • R-Value Work: 0.212 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 80.305α = 90
b = 123.577β = 90
c = 45.092γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
PHASERphasing
CNXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-12-26
    Type: Initial release
  • Version 2.0: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Polymer sequence, Refinement description, Structure summary
  • Version 3.0: 2023-11-15
    Changes: Atomic model, Data collection, Derived calculations