2je5
From Proteopedia
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|PDB= 2je5 |SIZE=350|CAPTION= <scene name='initialview01'>2je5</scene>, resolution 2.60Å | |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> | |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= | + | |LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=L4C:(2E)-2-{[(2S)-2-(ACETYLAMINO)-2-CARBOXYETHOXY]IMINO}PENTANEDIOIC+ACID'>L4C</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2bg1|2BG1]], [[2bg3|2BG3]], [[2bg4|2BG4]], [[2fff|2FFF]], [[2jch|2JCH]], [[2jci|2JCI]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2je5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2je5 OCA], [http://www.ebi.ac.uk/pdbsum/2je5 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2je5 RCSB]</span> | ||
}} | }} | ||
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[[Category: Schofield, C J.]] | [[Category: Schofield, C J.]] | ||
[[Category: Zervosen, A.]] | [[Category: Zervosen, A.]] | ||
| - | [[Category: CL]] | ||
| - | [[Category: L4C]] | ||
| - | [[Category: SO4]] | ||
[[Category: cell wall]] | [[Category: cell wall]] | ||
[[Category: drug-binding protein]] | [[Category: drug-binding protein]] | ||
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[[Category: peptidoglycan synthesis multifunctional enzyme]] | [[Category: peptidoglycan synthesis multifunctional enzyme]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:56:53 2008'' |
Revision as of 00:56, 31 March 2008
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| , resolution 2.60Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | , , , , , , and | ||||||
| Ligands: | , , | ||||||
| Related: | 2BG1, 2BG3, 2BG4, 2FFF, 2JCH, 2JCI
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| 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
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