5TZ8

Crystal structure of S. aureus TarS


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 4.00 Å
  • R-Value Free: 0.306 
  • R-Value Work: 0.280 
  • R-Value Observed: 0.281 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structure and Mechanism of Staphylococcus aureus TarS, the Wall Teichoic Acid beta-glycosyltransferase Involved in Methicillin Resistance.

Sobhanifar, S.Worrall, L.J.King, D.T.Wasney, G.A.Baumann, L.Gale, R.T.Nosella, M.Brown, E.D.Withers, S.G.Strynadka, N.C.

(2016) PLoS Pathog 12: e1006067-e1006067

  • DOI: https://doi.org/10.1371/journal.ppat.1006067
  • Primary Citation of Related Structures:  
    5TZ8, 5TZE, 5TZI, 5TZJ, 5TZK, 5U02

  • PubMed Abstract: 

    In recent years, there has been a growing interest in teichoic acids as targets for antibiotic drug design against major clinical pathogens such as Staphylococcus aureus, reflecting the disquieting increase in antibiotic resistance and the historical success of bacterial cell wall components as drug targets. It is now becoming clear that β-O-GlcNAcylation of S. aureus wall teichoic acids plays a major role in both pathogenicity and antibiotic resistance. Here we present the first structure of S. aureus TarS, the enzyme responsible for polyribitol phosphate β-O-GlcNAcylation. Using a divide and conquer strategy, we obtained crystal structures of various TarS constructs, mapping high resolution overlapping N-terminal and C-terminal structures onto a lower resolution full-length structure that resulted in a high resolution view of the entire enzyme. Using the N-terminal structure that encapsulates the catalytic domain, we furthermore captured several snapshots of TarS, including the native structure, the UDP-GlcNAc donor complex, and the UDP product complex. These structures along with structure-guided mutants allowed us to elucidate various catalytic features and identify key active site residues and catalytic loop rearrangements that provide a valuable platform for anti-MRSA drug design. We furthermore observed for the first time the presence of a trimerization domain composed of stacked carbohydrate binding modules, commonly observed in starch active enzymes, but adapted here for a poly sugar-phosphate glycosyltransferase.


  • Organizational Affiliation

    Department of Biochemistry and Center for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Glycosyl transferaseA,
B [auth C],
C [auth B]
572Staphylococcus aureusMutation(s): 0 
Gene Names: 
EC: 2.4.1
UniProt
Find proteins for A0A0H3JPC6 (Staphylococcus aureus (strain Mu50 / ATCC 700699))
Explore A0A0H3JPC6 
Go to UniProtKB:  A0A0H3JPC6
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A0H3JPC6
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 4.00 Å
  • R-Value Free: 0.306 
  • R-Value Work: 0.280 
  • R-Value Observed: 0.281 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 71.851α = 90
b = 191.468β = 109.5
c = 97.025γ = 90
Software Package:
Software NamePurpose
xia2data scaling
XDSdata reduction
PHENIXrefinement
PDB_EXTRACTdata extraction
Aimlessdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Canadian Institutes of Health Research (CIHR)Canada--
Howard Hughes Medical Institute (HHMI)United States--

Revision History  (Full details and data files)

  • Version 1.0: 2017-01-04
    Type: Initial release
  • Version 1.1: 2017-11-01
    Changes: Author supporting evidence, Refinement description
  • Version 1.2: 2019-11-20
    Changes: Author supporting evidence
  • Version 1.3: 2024-03-06
    Changes: Data collection, Database references