2jch

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[[Image:2jch.jpg|left|200px]]
[[Image:2jch.jpg|left|200px]]
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{{Structure
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<!--
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|PDB= 2jch |SIZE=350|CAPTION= <scene name='initialview01'>2jch</scene>, resolution 2.40&Aring;
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The line below this paragraph, containing "STRUCTURE_2jch", creates the "Structure Box" on the page.
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|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>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PL7:(2E)-2-({(2S)-2-CARBOXY-2-[(PHENOXYACETYL)AMINO]ETHOXY}IMINO)PENTANEDIOIC+ACID'>PL7</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY=
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or leave the SCENE parameter empty for the default display.
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|GENE=
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-->
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|DOMAIN=
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{{STRUCTURE_2jch| PDB=2jch | SCENE= }}
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|RELATEDENTRY=[[2bg1|2BG1]], [[2bg3|2BG3]], [[2bg4|2BG4]], [[2fff|2FFF]], [[2jci|2JCI]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2jch FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jch OCA], [http://www.ebi.ac.uk/pdbsum/2jch PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2jch RCSB]</span>
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}}
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'''STRUCTURAL AND MECHANISTIC BASIS OF PENICILLIN BINDING PROTEIN INHIBITION BY LACTIVICINS'''
'''STRUCTURAL AND MECHANISTIC BASIS OF PENICILLIN BINDING PROTEIN INHIBITION BY LACTIVICINS'''
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[[Category: Schofield, C J.]]
[[Category: Schofield, C J.]]
[[Category: Zervosen, A.]]
[[Category: Zervosen, A.]]
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[[Category: binding protein]]
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[[Category: Binding protein]]
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[[Category: cell wall]]
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[[Category: Cell wall]]
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[[Category: drug-binding protein]]
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[[Category: Drug-binding protein]]
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[[Category: gamma lactam antibiotic]]
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[[Category: Gamma lactam antibiotic]]
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[[Category: peptidoglycan]]
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[[Category: Peptidoglycan]]
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[[Category: peptidoglycan synthesis multifunctional enzyme]]
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[[Category: Peptidoglycan synthesis multifunctional enzyme]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 08:41:33 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:56:11 2008''
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Revision as of 05:41, 4 May 2008

Image:2jch.jpg

Template:STRUCTURE 2jch

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 Page seeded by OCA on Sun May 4 08:41:33 2008

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