4BL2: Crystal Structure Of Pbp2a Clinical Mutant E150k From Mrsa

Ceftaroline, a recently approved beta-lactam antibiotic for treatment of infections by methicillin-resistant Staphylococcus aureus (MRSA), is able to inhibit penicillin-binding protein 2a (PBP2a) by triggering an allosteric conformational change that leads to the opening of the active site. The opened active site is now vulnerable to inhibition by a second molecule of ceftaroline, an event that impairs cell-wall biosynthesis and leads to bacterial death. The triggering of the allosteric effect takes place by binding of the first antibiotic molecule 60 A away from the active site of PBP2a within the core of the allosteric site. We document, by kinetic studies and by determination of three X-ray structures of the mutant variants of PBP2a that result in resistance to ceftaroline, that the effect of these clinical mutants is the disruption of the allosteric trigger in this important protein in MRSA. This is an unprecedented mechanism for antibiotic resistance.
PDB ID: 4BL2Download
MMDB ID: 119999
PDB Deposition Date: 2013/4/30
Updated in MMDB: 2014/09
Experimental Method:
x-ray diffraction
Resolution: 2.72  Å
Source Organism:
Similar Structures:
Biological Unit for 4BL2: monomeric; determined by author and by software (PISA)
Molecular Components in 4BL2
Label Count Molecule
Protein (1 molecule)
Penicillin Binding Protein 2 Prime
Molecule annotation
Chemicals (8 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB