2WAF
PENICILLIN-BINDING PROTEIN 2B (PBP-2B) FROM STREPTOCOCCUS PNEUMONIAE (STRAIN R6)
Summary for 2WAF
| Entry DOI | 10.2210/pdb2waf/pdb |
| Related | 2WAD 2WAE |
| Descriptor | PENICILLIN-BINDING PROTEIN 2B, CHLORIDE ION (3 entities in total) |
| Functional Keywords | peptidoglycan synthesis, penicillin-binding protein, transmembrane, antibiotic resistance, cell shape, peptidoglycan, cell membrane, cell wall biogenesis/degradation, membrane, infection, resistance, antibiotic, peptide binding protein |
| Biological source | STREPTOCOCCUS PNEUMONIAE |
| Total number of polymer chains | 1 |
| Total formula weight | 74281.65 |
| Authors | Contreras-Martel, C.,Dahout-Gonzalez, C.,Dos-Santos-Martins, A.,Kotnik, M.,Dessen, A. (deposition date: 2009-02-05, release date: 2009-02-24, Last modification date: 2023-12-13) |
| Primary citation | Contreras-Martel, C.,Dahout-Gonzalez, C.,Dos-Santos-Martins, A.,Kotnik, M.,Dessen, A. Pbp Active Site Flexibility as the Key Mechanism for Beta-Lactam Resistance in Pneumococci J.Mol.Biol., 387:899-, 2009 Cited by PubMed Abstract: Penicillin-binding proteins (PBPs), the main targets of beta-lactam antibiotics, are membrane-associated enzymes that catalyze the two last steps in the biosynthesis of peptidoglycan. In Streptococcus pneumoniae, a major human pathogen, the surge in resistance to such antibiotics is a direct consequence of the proliferation of mosaic PBP-encoding genes, which give rise to proteins containing tens of mutations. PBP2b is a major drug resistance target, and its modification is essential for the development of high levels of resistance to piperacillin. In this work, we have solved the crystal structures of PBP2b from a wild-type pneumococcal strain, as well as from a highly drug-resistant clinical isolate displaying 58 mutations. Although mutations are present throughout the entire PBP structure, those surrounding the active site influence the total charge and the polar character of the region, while those in close proximity to the catalytic nucleophile impart flexibility onto the beta3/beta4 loop area, which encapsulates the cleft. The wealth of structural data on pneumococcal PBPs now underlines the importance of high malleability in active site regions of drug-resistant strains, suggesting that active site "breathing" could be a common mechanism employed by this pathogen to prevent targeting by beta-lactams. PubMed: 19233207DOI: 10.1016/J.JMB.2009.02.024 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.29 Å) |
Structure validation
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