1blc: Difference between revisions
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[[Image:1blc.gif|left|200px]] | [[Image:1blc.gif|left|200px]] | ||
'''INHIBITION OF BETA-LACTAMASE BY CLAVULANATE: TRAPPED INTERMEDIATES IN CRYOCRYSTALLOGRAPHIC STUDIES''' | {{Structure | ||
|PDB= 1blc |SIZE=350|CAPTION= <scene name='initialview01'>1blc</scene>, resolution 2.2Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=CEM:N-(1-CARBOXY-2-HYDROXY-4-OXO-BUTYL)-N-(3-OXO-CISPROPENYL)AMINE'>CEM</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] | |||
|GENE= | |||
}} | |||
'''INHIBITION OF BETA-LACTAMASE BY CLAVULANATE: TRAPPED INTERMEDIATES IN CRYOCRYSTALLOGRAPHIC STUDIES''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1BLC is a [ | 1BLC is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BLC OCA]. | ||
==Reference== | ==Reference== | ||
Inhibition of beta-lactamase by clavulanate. Trapped intermediates in cryocrystallographic studies., Chen CC, Herzberg O, J Mol Biol. 1992 Apr 20;224(4):1103-13. PMID:[http:// | Inhibition of beta-lactamase by clavulanate. Trapped intermediates in cryocrystallographic studies., Chen CC, Herzberg O, J Mol Biol. 1992 Apr 20;224(4):1103-13. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/1569569 1569569] | ||
[[Category: Beta-lactamase]] | [[Category: Beta-lactamase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: hydrolase(acting in cyclic amides)]] | [[Category: hydrolase(acting in cyclic amides)]] | ||
''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 10:12:38 2008'' | ||
Revision as of 11:12, 20 March 2008
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| , resolution 2.2Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Activity: | Beta-lactamase, with EC number 3.5.2.6 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
INHIBITION OF BETA-LACTAMASE BY CLAVULANATE: TRAPPED INTERMEDIATES IN CRYOCRYSTALLOGRAPHIC STUDIES
OverviewOverview
Crystallographic studies of the complex between beta-lactamase and clavulanate reveal a structure of two acyl-enzymes with covalent bonds at the active site Ser70, representing two different stages of inhibitor degradation alternately occupying the active site. Models that are consistent with biochemical data are derived from the electron density map and refined at 2.2 A resolution: cis enamine, in which the carboxylate group of the clavulanate molecule makes a salt bridge with Lys234 of beta-lactamase; decarboxylated trans enamine, which is oriented away from Lys234. For both acyl-enzymes, the carbonyl oxygen atom of the ester group occupies the oxyanion hole in a manner similar to that found in inhibitor binding to serine proteases. Whereas the oxygen atom in the trans product is optimally positioned in the oxyanion hole, that of the cis product clashes with the main-chain nitrogen atom of Ser70 and the beta-carbon atom of the adjacent Ala69. In contrast to cis to trans isomerization in solution that relieves the steric strain inherent in a cis double bond, at the enzyme-inhibitor interface two additional factors play an important role. The salt bridge enhances the stability of the cis product, while the steric strain introduced by the short contacts with the protein reduces its stability.
About this StructureAbout this Structure
1BLC is a Single protein structure of sequence from Staphylococcus aureus. Full crystallographic information is available from OCA.
ReferenceReference
Inhibition of beta-lactamase by clavulanate. Trapped intermediates in cryocrystallographic studies., Chen CC, Herzberg O, J Mol Biol. 1992 Apr 20;224(4):1103-13. PMID:1569569
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