1RP5

PBP2x from Streptococcus pneumoniae strain 5259 with reduced susceptibility to beta-lactam antibiotics


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.231 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

A PBP2x from a clinical isolate of Streptococcus pneumoniae exhibits an alternative mechanism for reduction of susceptibility to beta-lactam antibiotics.

Pernot, L.Chesnel, L.Le Gouellec, A.Croize, J.Vernet, T.Dideberg, O.Dessen, A.

(2004) J Biol Chem 279: 16463-16470

  • DOI: https://doi.org/10.1074/jbc.M313492200
  • Primary Citation of Related Structures:  
    1RP5

  • PubMed Abstract: 

    The human pathogen Streptococcus pneumoniae is one of the main causative agents of respiratory tract infections. At present, clinical isolates of S. pneumoniae often exhibit decreased susceptibility toward beta-lactams, a phenomenon linked to multiple mutations within the penicillin-binding proteins (PBPs). PBP2x, one of the six PBPs of S. pneumoniae, is the first target to be modified under antibiotic pressure. By comparing 89 S. pneumoniae PBP2x sequences from clinical and public data bases, we have identified one major group of sequences from drug-sensitive strains as well as two distinct groups from drug-resistant strains. The first group includes proteins that display high similarity to PBP2x from the well characterized resistant strain Sp328. The second group includes sequences in which a signature mutation, Q552E, is found adjacent to the third catalytic motif. In this work, a PBP2x from a representative strain from the latter group (S. pneumoniae 5259) was biochemically and structurally characterized. Phenotypical analyses of transformed pneumococci show that the Q552E substitution is responsible for most of the reduction of strain susceptibility toward beta-lactams. The crystal structure of 5259-PBP2x reveals a change in polarity and charge distribution around the active site cavity, as well as rearrangement of strand beta3, emulating structural changes observed for other PBPs that confer drug resistance to Gram-positive pathogens. Interestingly, the active site of 5259-PBP2x is in closed conformation, whereas that of Sp328-PBP2x is open. Consequently, S. pneumoniae has evolved to employ the same protein in two distinct mechanisms of antibiotic resistance.


  • Organizational Affiliation

    Laboratoire de Cristallographie Macromoléculaire, Institut de Biologie Structurale Jean-Pierre Ebel (CNRS/CEA/UJF), Grenoble, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
penicillin-binding protein 2x
A, B
702Streptococcus pneumoniaeMutation(s): 0 
Gene Names: PBP2X
EC: 3.4
UniProt
Find proteins for P14677 (Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4))
Explore P14677 
Go to UniProtKB:  P14677
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP14677
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.231 
  • Space Group: P 42 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 194.989α = 90
b = 194.989β = 90
c = 154.245γ = 90
Software Package:
Software NamePurpose
MOSFLMdata reduction
TRUNCATEdata reduction
MOLREPphasing
CNSrefinement
CCP4data scaling
AMoREphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-02-03
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-23
    Changes: Data collection, Database references, Derived calculations, Refinement description