2jch
From Proteopedia
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==Overview== | ==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 ... | + | 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== | ==About this Structure== | ||
| - | 2JCH is a | + | 2JCH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptococcus_pneumoniae_r6 Streptococcus pneumoniae r6] with SO4, CL, EDO and PL7 as [http://en.wikipedia.org/wiki/ligands ligands]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2JCH OCA]. |
==Reference== | ==Reference== | ||
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[[Category: peptidoglycan synthesis multifunctional enzyme]] | [[Category: peptidoglycan synthesis multifunctional enzyme]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 13:06:02 2007'' |
Revision as of 11:00, 5 November 2007
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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 with SO4, CL, EDO and PL7 as ligands. Structure known Active Site: AC1. 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 Aug 5;. PMID:17676039
Page seeded by OCA on Mon Nov 5 13:06:02 2007
Categories: Single protein | Streptococcus pneumoniae r6 | Brown, T.J. | Dessen, A. | Fisher, D.S. | Joris, B. | Luxen, A. | Macheboeuf, P. | Schofield, C.J. | Zervosen, A. | CL | EDO | PL7 | SO4 | Binding protein | Cell wall | Drug-binding protein | Gamma lactam antibiotics | Peptidoglycan | Peptidoglycan synthesis multifunctional enzyme
