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| | {{STRUCTURE_2jah| PDB=2jah | SCENE= }} | | {{STRUCTURE_2jah| PDB=2jah | SCENE= }} |
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| - | '''BIOCHEMICAL AND STRUCTURAL ANALYSIS OF THE CLAVULANIC ACID DEHYDEOGENASE (CAD) FROM STREPTOMYCES CLAVULIGERUS'''
| + | ===BIOCHEMICAL AND STRUCTURAL ANALYSIS OF THE CLAVULANIC ACID DEHYDEOGENASE (CAD) FROM STREPTOMYCES CLAVULIGERUS=== |
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| - | ==Overview==
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| - | 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. | + | The line below this paragraph, {{ABSTRACT_PUBMED_17279617}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 17279617 is the PubMed ID number. |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Oxidoreductase]] | | [[Category: Oxidoreductase]] |
| | [[Category: Short-chain dehydrogenase/reductase]] | | [[Category: Short-chain dehydrogenase/reductase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 08:36:19 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 15:31:41 2008'' |
Revision as of 12:31, 27 July 2008
Template:STRUCTURE 2jah
BIOCHEMICAL AND STRUCTURAL ANALYSIS OF THE CLAVULANIC ACID DEHYDEOGENASE (CAD) FROM STREPTOMYCES CLAVULIGERUS
Template:ABSTRACT PUBMED 17279617
About this Structure
2JAH is a Single protein structure of sequence from Streptomyces clavuligerus. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Sun Jul 27 15:31:41 2008
