2jap: Difference between revisions
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[[Image:2jap. | [[Image:2jap.jpg|left|200px]]<br /><applet load="2jap" size="450" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2jap" size="450" color="white" frame="true" align="right" spinBox="true" | |||
caption="2jap, resolution 2.10Å" /> | caption="2jap, resolution 2.10Å" /> | ||
'''CLAVULANIC ACID DEHYDROGENASE: STRUCTURAL AND BIOCHEMICAL ANALYSIS OF THE FINAL STEP IN THE BIOSYNTHESIS OF THE BETA-LACTAMASE INHIBITOR CLAVULANIC ACID'''<br /> | '''CLAVULANIC ACID DEHYDROGENASE: STRUCTURAL AND BIOCHEMICAL ANALYSIS OF THE FINAL STEP IN THE BIOSYNTHESIS OF THE BETA-LACTAMASE INHIBITOR CLAVULANIC ACID'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
2JAP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_clavuligerus Streptomyces clavuligerus] with NDP and J01 as [http://en.wikipedia.org/wiki/ligands ligands]. | 2JAP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_clavuligerus Streptomyces clavuligerus] with NDP and J01 as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Site: <scene name='pdbsite=AC1:J01 Binding Site For Chain D'>AC1</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2JAP OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: short-chain dehydrogenase/reductase]] | [[Category: short-chain dehydrogenase/reductase]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 19:58:06 2007'' | ||
Revision as of 20:48, 18 December 2007
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CLAVULANIC ACID DEHYDROGENASE: STRUCTURAL AND BIOCHEMICAL ANALYSIS OF THE FINAL STEP IN THE BIOSYNTHESIS OF THE BETA-LACTAMASE INHIBITOR CLAVULANIC ACID
OverviewOverview
The ultimate step in the biosynthesis of the medicinally important, beta-lactamase inhibitor clavulanic acid is catalyzed by clavulanic acid, dehydrogenase (CAD). CAD is responsible for the NAPDH-dependent reduction, of the unstable intermediate clavulanate-9-aldehyde to yield clavulanic, acid. Here, we report biochemical and structural studies on CAD., Biophysical analyses demonstrate that CAD exists as dimeric and tetrameric, species in solution. The reaction performed by CAD was shown to be, reversible, allowing the use of clavulanic acid for activity analyses. The, crystal structure of CAD was solved using single-wavelength anomalous, diffraction with a seleno-methionine derivative. The structure reveals, that the individual monomers comprise a single domain possessing the, Rossmann fold, characteristic of dinucleotide-binding enzymes. The, monomers are arranged as tetramers, similar to other tetrameric members of, the short-chain dehydrogenase/reductase family. The structure of the, unreactive complex of CAD with clavulanic acid and NADPH suggests how CAD, is able to catalyze the reduction of clavulanate-9-aldehyde without, fragmentation of the bicyclic beta-lactam ring structure. The relative, positions of NADPH and clavulanic acid, in the active site, together with, the presence of the latter in an eclipsed conformation, rationalizes, previous labeling studies demonstrating that the incorporation of the C5, pro-R, but not pro-S, hydrogen of ornithine/arginine into the C9 position, of clavulanic acid occurs with overall inversion of configuration.
About this StructureAbout this Structure
2JAP is a Single protein structure of sequence from Streptomyces clavuligerus with NDP and J01 as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Clavulanic acid dehydrogenase: structural and biochemical analysis of the final step in the biosynthesis of the beta-lactamase inhibitor clavulanic acid., MacKenzie AK, Kershaw NJ, Hernandez H, Robinson CV, Schofield CJ, Andersson I, Biochemistry. 2007 Feb 13;46(6):1523-33. Epub 2007 Jan 19. PMID:17279617
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