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| | <StructureSection load='2jah' size='340' side='right'caption='[[2jah]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='2jah' size='340' side='right'caption='[[2jah]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2jah]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/As_4.1611 As 4.1611]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JAH OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2JAH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2jah]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_clavuligerus Streptomyces clavuligerus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JAH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JAH FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2jah FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jah OCA], [http://pdbe.org/2jah PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2jah RCSB], [http://www.ebi.ac.uk/pdbsum/2jah PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2jah ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2jah FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jah OCA], [https://pdbe.org/2jah PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jah RCSB], [https://www.ebi.ac.uk/pdbsum/2jah PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jah ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ja/2jah_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ja/2jah_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: As 4 1611]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Andersson, I]] | + | [[Category: Streptomyces clavuligerus]] |
| - | [[Category: Hernandez, H]] | + | [[Category: Andersson I]] |
| - | [[Category: Kershaw, N J]] | + | [[Category: Hernandez H]] |
| - | [[Category: MacKenzie, A K]] | + | [[Category: Kershaw NJ]] |
| - | [[Category: Robinson, C V]] | + | [[Category: MacKenzie AK]] |
| - | [[Category: Schofield, C J]] | + | [[Category: Robinson CV]] |
| - | [[Category: Antibiotic biosynthesis]]
| + | [[Category: Schofield CJ]] |
| - | [[Category: Clavulanic acid]]
| + | |
| - | [[Category: Lactamase inhibitor]]
| + | |
| - | [[Category: Nadph]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Short-chain dehydrogenase/reductase]]
| + | |
| Structural highlights
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ MacKenzie AK, Kershaw NJ, Hernandez H, Robinson CV, Schofield CJ, Andersson I. Clavulanic acid dehydrogenase: structural and biochemical analysis of the final step in the biosynthesis of the beta-lactamase inhibitor clavulanic acid. Biochemistry. 2007 Feb 13;46(6):1523-33. Epub 2007 Jan 19. PMID:17279617 doi:10.1021/bi061978x
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