1K25

PBP2x from a Highly Penicillin-resistant Streptococcus pneumoniae Clinical Isolate


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.20 Å
  • R-Value Free: 0.312 
  • R-Value Work: 0.235 
  • R-Value Observed: 0.235 

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This is version 1.5 of the entry. See complete history


Literature

Crystal structure of PBP2x from a highly penicillin-resistant Streptococcus pneumoniae clinical isolate: a mosaic framework containing 83 mutations.

Dessen, A.Mouz, N.Gordon, E.Hopkins, J.Dideberg, O.

(2001) J Biol Chem 276: 45106-45112

  • DOI: https://doi.org/10.1074/jbc.M107608200
  • Primary Citation of Related Structures:  
    1K25

  • PubMed Abstract: 

    Penicillin-binding proteins (PBPs) are the main targets for beta-lactam antibiotics, such as penicillins and cephalosporins, in a wide range of bacterial species. In some Gram-positive strains, the surge of resistance to treatment with beta-lactams is primarily the result of the proliferation of mosaic PBP-encoding genes, which encode novel proteins by recombination. PBP2x is a primary resistance determinant in Streptococcus pneumoniae, and its modification is an essential step in the development of high level beta-lactam resistance. To understand such a resistance mechanism at an atomic level, we have solved the x-ray crystal structure of PBP2x from a highly penicillin-resistant clinical isolate of S. pneumoniae, Sp328, which harbors 83 mutations in the soluble region. In the proximity of the Sp328 PBP2x* active site, the Thr(338) --> Ala mutation weakens the local hydrogen bonding network, thus abrogating the stabilization of a crucial buried water molecule. In addition, the Ser(389) --> Leu and Asn(514) --> His mutations produce a destabilizing effect that generates an "open" active site. It has been suggested that peptidoglycan substrates for beta-lactam-resistant PBPs contain a large amount of abnormal, branched peptides, whereas sensitive strains tend to catalyze cross-linking of linear forms. Thus, in vivo, an "open" active site could facilitate the recognition of distinct, branched physiological substrates.


  • Organizational Affiliation

    Laboratoire de Cristallographie Macromoléculaire, Institut de Biologie Structurale Jean-Pierre Ebel (CNRS/Commissariat à l'Energie Atomique), 41, rue Jules Horowitz, 38027 Grenoble, France. [email protected]


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
low-affinity PENICILLIN-BINDING PROTEIN 2X
A, B, C, D
685Streptococcus pneumoniaeMutation(s): 1 
UniProt
Find proteins for O34006 (Streptococcus pneumoniae)
Explore O34006 
Go to UniProtKB:  O34006
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO34006
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.20 Å
  • R-Value Free: 0.312 
  • R-Value Work: 0.235 
  • R-Value Observed: 0.235 
  • Space Group: P 32
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 146.56α = 90
b = 146.56β = 90
c = 132.61γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing
CNSrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2001-10-31
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2018-01-31
    Changes: Experimental preparation
  • Version 1.4: 2021-10-27
    Changes: Database references
  • Version 1.5: 2024-02-07
    Changes: Data collection