1rp5
From Proteopedia
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PBP2x from Streptococcus pneumoniae strain 5259 with reduced susceptibility to beta-lactam antibiotics
Overview
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.
About this Structure
1RP5 is a Single protein structure of sequence from Streptococcus pneumoniae with SO4 as ligand. Full crystallographic information is available from OCA.
Reference
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, J Biol Chem. 2004 Apr 16;279(16):16463-70. Epub 2004 Jan 20. PMID:14734544
Page seeded by OCA on Wed Nov 21 01:45:53 2007
