4cpk | pdb_00004cpk

Crystal structure of PBP2a double clinical mutant N146K-E150K from MRSA

spinqualitylabelsall models 4cpk, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4cpk is a 2 chain structure with sequence from Staam. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CD, CL, MUR Activity: Serine-type D-Ala-D-Ala carboxypeptidase, with EC number 3.4.16.4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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. Disruption of allosteric response as an unprecedented mechanism of resistance to antibiotics.,Fishovitz J, Rojas-Altuve A, Otero LH, Dawley M, Carrasco-Lopez C, Chang M, Hermoso JA, Mobashery S J Am Chem Soc. 2014 Jul 16;136(28):9814-7. doi: 10.1021/ja5030657. Epub 2014 Jul , 2. PMID:24955778 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Penicillin-binding protein 3D structures

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