3HZS

S. aureus monofunctional glycosyltransferase (MtgA)in complex with moenomycin


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.189 
  • R-Value Observed: 0.192 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Characterization of the active site of S. aureus monofunctional glycosyltransferase (Mtg) by site-directed mutation and structural analysis of the protein complexed with moenomycin

Heaslet, H.Shaw, B.Mistry, A.Miller, A.A.

(2009) J Struct Biol 167: 129-135

  • DOI: https://doi.org/10.1016/j.jsb.2009.04.010
  • Primary Citation of Related Structures:  
    3HZS

  • PubMed Abstract: 

    Bacterial cell wall transglycosylases (TGs) and transpeptidases (TPs) are ideal drug targets due to their essentiality, accessibility and lack of mammalian homologs. Although antibacterial therapy using the beta-lactam family of TP inhibitors has been successful for decades, potent TG inhibitors which are suitable for development into antibiotics for human use have yet to be identified. We sought to further understand the molecular interactions required to inhibit bacterial transglycosylation by characterizing the active site of Staphylococcus aureus (Sa) monofunctional transglycosylase (Mtg). Ten mutants were tested for their ability to polymerize Lipid II and to crystallize in the presence of moenomycin. Five of six putative active site mutants (E100Q, D101N, Q136E, E156T, and Y176F) were found to be catalytically inactive whereas a F104Y mutation did not affect activity. Four mutants generated to enhance crystal formation (F143T, V154T, L157T, and F158T) also retained activity. Here we also report the crystal structure of Sa Mtg E100Q mutant in complex with the inhibitor moenomycin to 2.1A resolution. The co-crystal structure revealed detailed interactions between the protein and inhibitor including portions of the polycarbon tail of moenomycin. The structure also contained an ordered phosphate ion which helped to identify the Lipid II binding site.


  • Organizational Affiliation

    Antibacterial Discovery Chemistry, Pfizer Global Research & Development, Groton, CT 06340, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Monofunctional glycosyltransferase209Staphylococcus aureus subsp. aureus MW2Mutation(s): 1 
Gene Names: mgtMW1814
EC: 2.4
Membrane Entity: Yes 
UniProt
Find proteins for Q7A0I6 (Staphylococcus aureus (strain MW2))
Explore Q7A0I6 
Go to UniProtKB:  Q7A0I6
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ7A0I6
Sequence Annotations
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  • Reference Sequence
Small Molecules
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.189 
  • R-Value Observed: 0.192 
  • Space Group: H 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 114.422α = 90
b = 114.422β = 90
c = 128.844γ = 120
Software Package:
Software NamePurpose
CrystalCleardata collection
AMoREphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-07-07
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Source and taxonomy, Version format compliance
  • Version 1.2: 2012-07-25
    Changes: Other
  • Version 1.3: 2021-10-13
    Changes: Database references, Derived calculations
  • Version 1.4: 2024-02-21
    Changes: Data collection