5KH2

Crystal Structure of Steptococcus pneumoniae Undecaprenyl pyrophosphate Synthase (UPPS)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.214 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Discovery and Characterization of a Class of Pyrazole Inhibitors of Bacterial Undecaprenyl Pyrophosphate Synthase.

Concha, N.Huang, J.Bai, X.Benowitz, A.Brady, P.Grady, L.C.Kryn, L.H.Holmes, D.Ingraham, K.Jin, Q.Pothier Kaushansky, L.McCloskey, L.Messer, J.A.O'Keefe, H.Patel, A.Satz, A.L.Sinnamon, R.H.Schneck, J.Skinner, S.R.Summerfield, J.Taylor, A.Taylor, J.D.Evindar, G.Stavenger, R.A.

(2016) J Med Chem 59: 7299-7304

  • DOI: https://doi.org/10.1021/acs.jmedchem.6b00746
  • Primary Citation of Related Structures:  
    5KH2, 5KH4, 5KH5

  • PubMed Abstract: 

    Undecaprenyl pyrophosphate synthase (UppS) is an essential enzyme in bacterial cell wall synthesis. Here we report the discovery of Staphylococcus aureus UppS inhibitors from an Encoded Library Technology screen and demonstrate binding to the hydrophobic substrate site through cocrystallography studies. The use of bacterial strains with regulated uppS expression and inhibitor resistant mutant studies confirmed that the whole cell activity was the result of UppS inhibition, validating UppS as a druggable antibacterial target.


  • Organizational Affiliation

    GlaxoSmithKline , 1250 S. Collegeville Road, Collegeville, Pennsylvania 19426, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Isoprenyl transferase
A, B, C, D
272Streptococcus pneumoniae TIGR4Mutation(s): 0 
Gene Names: uppSSP_0261
EC: 2.5.1
UniProt
Find proteins for Q97SR4 (Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4))
Explore Q97SR4 
Go to UniProtKB:  Q97SR4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ97SR4
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.214 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 59.687α = 90
b = 118.029β = 90
c = 178.326γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling
SOLVEphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2016-07-20 
  • Deposition Author(s): Concha, N.O.

Revision History  (Full details and data files)

  • Version 1.0: 2016-07-20
    Type: Initial release
  • Version 1.1: 2016-08-24
    Changes: Database references
  • Version 1.2: 2019-03-13
    Changes: Data collection, Database references, Derived calculations
  • Version 1.3: 2024-03-06
    Changes: Data collection, Database references