1xgj: Difference between revisions

Revision as of 02:09, 28 July 2008

This article has been automatically seeded. Changes to this page should pertain to the PDB entry only and not to the protein or biomolecule in general.

File:1xgj.png

Template:STRUCTURE 1xgj

AmpC beta-lactamase in complex with 3-(4-carboxy-2-hydroxy-phenylsulfamoyl)-thiophene-2-carboxylic acidAmpC beta-lactamase in complex with 3-(4-carboxy-2-hydroxy-phenylsulfamoyl)-thiophene-2-carboxylic acid

Template:ABSTRACT PUBMED 15796528

About this StructureAbout this Structure

1XGJ is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

ReferenceReference

Structure-based optimization of a non-beta-lactam lead results in inhibitors that do not up-regulate beta-lactamase expression in cell culture., Tondi D, Morandi F, Bonnet R, Costi MP, Shoichet BK, J Am Chem Soc. 2005 Apr 6;127(13):4632-9. PMID:15796528

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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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-'''AmpC beta-lactamase in complex with 3-(4-carboxy-2-hydroxy-phenylsulfamoyl)-thiophene-2-carboxylic acid'''
+===AmpC beta-lactamase in complex with 3-(4-carboxy-2-hydroxy-phenylsulfamoyl)-thiophene-2-carboxylic acid===
-==Overview==
+<!--
-Bacterial expression of beta-lactamases is the most widespread resistance mechanism to beta-lactam antibiotics, such as penicillins and cephalosporins. There is a pressing need for novel, non-beta-lactam inhibitors of these enzymes. One previously discovered novel inhibitor of the beta-lactamase AmpC, compound 1, has several favorable properties: it is chemically dissimilar to beta-lactams and is a noncovalent, competitive inhibitor of the enzyme. However, at 26 microM its activity is modest. Using the X-ray structure of the AmpC/1 complex as a template, 14 analogues were designed and synthesized. The most active of these, compound 10, had a K(i) of 1 microM, 26-fold better than the lead. To understand the origins of this improved activity, the structures of AmpC in complex with compound 10 and an analogue, compound 11, were determined by X-ray crystallography to 1.97 and 1.96 A, respectively. Compound 10 was active in cell culture, reversing resistance to the third generation cephalosporin ceftazidime in bacterial pathogens expressing AmpC. In contrast to beta-lactam-based inhibitors clavulanate and cefoxitin, compound 10 did not up-regulate beta-lactamase expression in cell culture but simply inhibited the enzyme expressed by the resistant bacteria. Its escape from this resistance mechanism derives from its dissimilarity to beta-lactam antibiotics.
+The line below this paragraph, {{ABSTRACT_PUBMED_15796528}}, adds the Publication Abstract to the page
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+{{ABSTRACT_PUBMED_15796528}}
 ==About this Structure==
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 [[Category: Cephalosporinase]]
 [[Category: Serine hydrolase]]
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