2je5
From Proteopedia
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| - | [[Image:2je5.jpg|left|200px]] | + | [[Image:2je5.jpg|left|200px]] |
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| - | '''STRUCTURAL AND MECHANISTIC BASIS OF PENICILLIN BINDING PROTEIN INHIBITION BY LACTIVICINS''' | + | {{Structure |
| + | |PDB= 2je5 |SIZE=350|CAPTION= <scene name='initialview01'>2je5</scene>, resolution 2.60Å | ||
| + | |SITE= <scene name='pdbsite=AC1:L4c+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:L4c+Binding+Site+For+Chain+B'>AC2</scene>, <scene name='pdbsite=AC3:So4+Binding+Site+For+Chain+B'>AC3</scene>, <scene name='pdbsite=AC4:So4+Binding+Site+For+Chain+A'>AC4</scene>, <scene name='pdbsite=AC5:Cl+Binding+Site+For+Chain+A'>AC5</scene>, <scene name='pdbsite=AC6:Cl+Binding+Site+For+Chain+A'>AC6</scene>, <scene name='pdbsite=AC7:Cl+Binding+Site+For+Chain+B'>AC7</scene> and <scene name='pdbsite=AC8:Cl+Binding+Site+For+Chain+B'>AC8</scene> | ||
| + | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene> and <scene name='pdbligand=L4C:(2E)-2-{[(2S)-2-(ACETYLAMINO)-2-CARBOXYETHOXY]IMINO}PENTANEDIOIC ACID'>L4C</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''STRUCTURAL AND MECHANISTIC BASIS OF PENICILLIN BINDING PROTEIN INHIBITION BY LACTIVICINS''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2JE5 is a [ | + | 2JE5 is a [[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=2JE5 OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/17676039 17676039] |
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Streptococcus pneumoniae]] | [[Category: Streptococcus pneumoniae]] | ||
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[[Category: cell wall]] | [[Category: cell wall]] | ||
[[Category: drug-binding protein]] | [[Category: drug-binding protein]] | ||
| - | [[Category: gamma lactam | + | [[Category: gamma lactam antibiotic]] |
[[Category: peptidoglycan]] | [[Category: peptidoglycan]] | ||
[[Category: peptidoglycan synthesis multifunctional enzyme]] | [[Category: peptidoglycan synthesis multifunctional enzyme]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:40:47 2008'' |
Revision as of 15:40, 20 March 2008
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| , resolution 2.60Å | |||||||
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| Sites: | , , , , , , and | ||||||
| Ligands: | , and | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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
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
Page seeded by OCA on Thu Mar 20 17:40:47 2008
Categories: Single protein | Streptococcus pneumoniae | Brown, T J. | Dessen, A. | Fisher, D S. | Joris, B. | Luxen, A. | Macheboeuf, P. | Schofield, C J. | Zervosen, A. | CL | L4C | SO4 | Cell wall | Drug-binding protein | Gamma lactam antibiotic | Peptidoglycan | Peptidoglycan synthesis multifunctional enzyme
