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1k25
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(New page: 200px<br /><applet load="1k25" size="450" color="white" frame="true" align="right" spinBox="true" caption="1k25, resolution 3.20Å" /> '''PBP2x from a Highly ...)
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Revision as of 22:27, 24 November 2007
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PBP2x from a Highly Penicillin-resistant Streptococcus pneumoniae Clinical Isolate
Overview
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.
About this Structure
1K25 is a Single protein structure of sequence from Streptococcus pneumoniae. Full crystallographic information is available from OCA.
Reference
Crystal structure of PBP2x from a highly penicillin-resistant Streptococcus pneumoniae clinical isolate: a mosaic framework containing 83 mutations., Dessen A, Mouz N, Gordon E, Hopkins J, Dideberg O, J Biol Chem. 2001 Nov 30;276(48):45106-12. Epub 2001 Sep 11. PMID:11553637
Page seeded by OCA on Sun Nov 25 00:35:24 2007
