1k25: Difference between revisions
New page: left|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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[[Image:1k25.jpg|left|200px]]<br /><applet load="1k25" size=" | [[Image:1k25.jpg|left|200px]]<br /><applet load="1k25" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1k25, resolution 3.20Å" /> | caption="1k25, resolution 3.20Å" /> | ||
'''PBP2x from a Highly Penicillin-resistant Streptococcus pneumoniae Clinical Isolate'''<br /> | '''PBP2x from a Highly Penicillin-resistant Streptococcus pneumoniae Clinical Isolate'''<br /> | ||
==Overview== | ==Overview== | ||
Penicillin-binding proteins (PBPs) are the main targets for beta-lactam | 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== | ==About this Structure== | ||
1K25 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae]. Full crystallographic information is available from [http:// | 1K25 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K25 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: low-affinity penicillin-binding]] | [[Category: low-affinity penicillin-binding]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:29:17 2008'' | ||
Revision as of 14:29, 21 February 2008
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PBP2x from a Highly Penicillin-resistant Streptococcus pneumoniae Clinical Isolate
OverviewOverview
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 StructureAbout this Structure
1K25 is a Single protein structure of sequence from Streptococcus pneumoniae. Full crystallographic information is available from OCA.
ReferenceReference
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
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