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| {{STRUCTURE_1k25| PDB=1k25 | SCENE= }} | | {{STRUCTURE_1k25| PDB=1k25 | SCENE= }} |
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| '''PBP2x from a Highly Penicillin-resistant Streptococcus pneumoniae Clinical Isolate'''
| | ===PBP2x from a Highly Penicillin-resistant Streptococcus pneumoniae Clinical Isolate=== |
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| ==Overview==
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| Penicillin-binding proteins (PBPs) are the main targets for beta-lactam antibiotics, such as penicillins and cephalosporins, in a wide range of bacterial species. In some Gram-positive strains, the surge of resistance to treatment with beta-lactams is primarily the result of the proliferation of mosaic PBP-encoding genes, which encode novel proteins by recombination. PBP2x is a primary resistance determinant in Streptococcus pneumoniae, and its modification is an essential step in the development of high level beta-lactam resistance. To understand such a resistance mechanism at an atomic level, we have solved the x-ray crystal structure of PBP2x from a highly penicillin-resistant clinical isolate of S. pneumoniae, Sp328, which harbors 83 mutations in the soluble region. In the proximity of the Sp328 PBP2x* active site, the Thr(338) --> Ala mutation weakens the local hydrogen bonding network, thus abrogating the stabilization of a crucial buried water molecule. In addition, the Ser(389) --> Leu and Asn(514) --> His mutations produce a destabilizing effect that generates an "open" active site. It has been suggested that peptidoglycan substrates for beta-lactam-resistant PBPs contain a large amount of abnormal, branched peptides, whereas sensitive strains tend to catalyze cross-linking of linear forms. Thus, in vivo, an "open" active site could facilitate the recognition of distinct, branched physiological substrates.
| | The line below this paragraph, {{ABSTRACT_PUBMED_11553637}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 11553637 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_11553637}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Clinical mutant]] | | [[Category: Clinical mutant]] |
| [[Category: Low-affinity penicillin-binding]] | | [[Category: Low-affinity penicillin-binding]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 22:12:23 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 21:24:43 2008'' |
