2y2p

Penicillin-binding protein 1b (pbp-1b) in complex with an alkyl boronate (z10)

spinqualitylabelsall models 2y2p, resolution 1.62Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2y2p is a 1 chain structure with sequence from Strr6. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, NA, Z10 Related: 2uwx, 2y2i, 2y2g, 2y2h, 2y2o, 2y2n, 2y2j, 2y2m, 2y2k, 2xd1, 2y2q, 2xd5, 2y2l Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed beta-Lactam antibiotics have long been a treatment of choice for bacterial infections since they bind irreversibly to Penicillin-Binding Proteins (PBPs), enzymes that are vital for cell wall biosynthesis. Many pathogens express drug-insensitive PBPs rendering beta-lactams ineffective, revealing a need for new types of PBP inhibitors active against resistant strains. We have identified alkyl boronic acids that are active against pathogens including methicillin-resistant S. aureus (MRSA). The crystal structures of PBP1b complexed to eleven different alkyl boronates demonstrate that in vivo efficacy correlates with the mode of inhibitor side chain binding. Staphylococcal membrane analyses reveal that the most potent alkyl boronate targets PBP1, an autolysis system regulator, and PBP2a, a low beta-lactam affinity enzyme. This work demonstrates the potential of boronate-based PBP-inhibitors for circumventing beta-lactam resistance, and opens avenues for the development of novel antibiotics that target Gram-positive pathogens. Structure-guided design of cell wall biosynthesis inhibitors that overcome beta-lactam resistance in Staphylococcus aureus (MRSA).,Contreras-Martel C, Amoroso A, Woon EC, Zervosen A, Inglis S, Martins A, Verlaine O, Rydzik A, Job V, Luxen A, Joris B, Schofield CJ, Dessen A ACS Chem Biol. 2011 Jul 6. PMID:21732689 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Penicillin-binding protein

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