2je5

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{{STRUCTURE_2je5| PDB=2je5 | SCENE= }}
{{STRUCTURE_2je5| PDB=2je5 | SCENE= }}
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'''STRUCTURAL AND MECHANISTIC BASIS OF PENICILLIN BINDING PROTEIN INHIBITION BY LACTIVICINS'''
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===STRUCTURAL AND MECHANISTIC BASIS OF PENICILLIN BINDING PROTEIN INHIBITION BY LACTIVICINS===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_17676039}}
==About this Structure==
==About this Structure==
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[[Category: Peptidoglycan]]
[[Category: Peptidoglycan]]
[[Category: Peptidoglycan synthesis multifunctional enzyme]]
[[Category: Peptidoglycan synthesis multifunctional enzyme]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 08:46:10 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 16:30:21 2008''

Revision as of 13:30, 27 July 2008

Image:2je5.png

Template:STRUCTURE 2je5

STRUCTURAL AND MECHANISTIC BASIS OF PENICILLIN BINDING PROTEIN INHIBITION BY LACTIVICINS

Template:ABSTRACT PUBMED 17676039

About this Structure

2JE5 is a Single protein structure of sequence from Streptococcus pneumoniae. 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

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