2jch: Difference between revisions
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[[Image:2jch.jpg|left|200px]] | [[Image:2jch.jpg|left|200px]] | ||
'''STRUCTURAL AND MECHANISTIC BASIS OF PENICILLIN BINDING PROTEIN INHIBITION BY LACTIVICINS''' | {{Structure | ||
|PDB= 2jch |SIZE=350|CAPTION= <scene name='initialview01'>2jch</scene>, resolution 2.40Å | |||
|SITE= <scene name='pdbsite=AC1:Pl7+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:So4+Binding+Site+For+Chain+A'>AC2</scene>, <scene name='pdbsite=AC3:Cl+Binding+Site+For+Chain+A'>AC3</scene> and <scene name='pdbsite=AC4:Edo+Binding+Site+For+Chain+A'>AC4</scene> | |||
|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene> and <scene name='pdbligand=PL7:(2E)-2-({(2S)-2-CARBOXY-2-[(PHENOXYACETYL)AMINO]ETHOXY}IMINO)PENTANEDIOIC ACID'>PL7</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== | ||
2JCH is a [ | 2JCH is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Streptococcus_pneumoniae_r6 Streptococcus pneumoniae r6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JCH 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 r6]] | [[Category: Streptococcus pneumoniae r6]] | ||
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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 17:40:04 2008'' | ||
Revision as of 15:40, 20 March 2008
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| 2jch, resolution 2.40Å | |||||||||||||
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| Sites: | AC1, AC2, AC3 and AC4 | ||||||||||||
| Ligands: | SO4, CL, EDO and PL7 | ||||||||||||
| 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
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
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