| Structural highlights
2y2q is a 2 chain structure with sequence from Streptococcus pneumoniae R6. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| Method: | X-ray diffraction, Resolution 2.15Å |
Ligands: | , , , , |
Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
Q7CRA4_STRR6
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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. Structure-guided design of cell wall biosynthesis inhibitors that overcome beta-lactam resistance in Staphylococcus aureus (MRSA). ACS Chem Biol. 2011 Jul 6. PMID:21732689 doi:10.1021/cb2001846
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