2jch: Difference between revisions
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{{STRUCTURE_2jch| PDB=2jch | SCENE= }} | |||
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'''STRUCTURAL AND MECHANISTIC BASIS OF PENICILLIN BINDING PROTEIN INHIBITION BY LACTIVICINS''' | '''STRUCTURAL AND MECHANISTIC BASIS OF PENICILLIN BINDING PROTEIN INHIBITION BY LACTIVICINS''' | ||
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[[Category: Schofield, C J.]] | [[Category: Schofield, C J.]] | ||
[[Category: Zervosen, A.]] | [[Category: Zervosen, A.]] | ||
[[Category: | [[Category: Binding protein]] | ||
[[Category: | [[Category: Cell wall]] | ||
[[Category: | [[Category: Drug-binding protein]] | ||
[[Category: | [[Category: Gamma lactam antibiotic]] | ||
[[Category: | [[Category: Peptidoglycan]] | ||
[[Category: | [[Category: Peptidoglycan synthesis multifunctional enzyme]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 08:41:33 2008'' | |||
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Revision as of 05:41, 4 May 2008
STRUCTURAL AND MECHANISTIC BASIS OF PENICILLIN BINDING PROTEIN INHIBITION BY LACTIVICINS
Overview
Beta-lactam antibiotics, including penicillins and cephalosporins, inhibit penicillin-binding proteins (PBPs), which are essential for bacterial cell wall biogenesis. Pathogenic bacteria have evolved efficient antibiotic resistance mechanisms that, in Gram-positive bacteria, include mutations to PBPs that enable them to avoid beta-lactam inhibition. Lactivicin (LTV; 1) contains separate cycloserine and gamma-lactone rings and is the only known natural PBP inhibitor that does not contain a beta-lactam. Here we show that LTV and a more potent analog, phenoxyacetyl-LTV (PLTV; 2), are active against clinically isolated, penicillin-resistant Streptococcus pneumoniae strains. Crystallographic analyses of S. pneumoniae PBP1b reveal that LTV and PLTV inhibition involves opening of both monocyclic cycloserine and gamma-lactone rings. In PBP1b complexes, the ring-derived atoms from LTV and PLTV show a notable structural convergence with those derived from a complexed cephalosporin (cefotaxime; 3). The structures imply that derivatives of LTV will be useful in the search for new antibiotics with activity against beta-lactam-resistant bacteria.
About this Structure
2JCH is a Single protein structure of sequence from Streptococcus pneumoniae r6. Full crystallographic information is available from OCA.
Reference
Structural and mechanistic basis of penicillin-binding protein inhibition by lactivicins., Macheboeuf P, Fischer DS, Brown T Jr, Zervosen A, Luxen A, Joris B, Dessen A, Schofield CJ, Nat Chem Biol. 2007 Sep;3(9):565-9. Epub 2007 Aug 5. PMID:17676039 Page seeded by OCA on Sun May 4 08:41:33 2008
