Structural highlights
Function
CAMK_RHOSO Catalyzes the carbon-carbon bond cleavage of the bicyclic beta-diketone 6-oxocamphor via a retro-Claisen reaction to yield the optically active (2R,4S)-beta-campholinic acid. It is also able to cleave 2,2-disubstituted cyclohexa-1,3-diones such as 2-methyl-2-propylcyclohexa-1,3-dione and 2-methyl-2-butylcyclohexa-1,3-dione which result in racemic keto acid products. Transformations of the bicyclic diketone substrates bicyclo[2.2.1]heptane 2,6-dione and bicyclo[2.2.2]octane-2,6-dione yield (S)-keto acid products.[1] [2]
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
6-Oxo camphor hydrolase (OCH) is an enzyme of the crotonase superfamily that catalyzes carbon-carbon bond cleavage in bicyclic beta-diketones via a retro-Claisen reaction (Grogan, G., Roberts, G. A., Bougioukou, D., Turner, N. J., and Flitsch, S. L. (2001) J. Biol. Chem. 276, 12565-12572). The native structure of OCH has been solved at 2.0-A resolution with selenomethionine multiple wave anomalous dispersion and refined to a final R(free) of 19.0. The structure of OCH consists of a dimer of trimers that resembles the "parent" enzyme of the superfamily, enoyl-CoA hydratase. In contrast to enoyl-CoA hydratase, however, two octahedrally coordinated sodium atoms are found at the 3-fold axis of the hexamer of OCH, and the C-terminal helix of OCH does not form a discrete domain. Models of the substrate, 6-oxo camphor, and a proposed enolate intermediate in the putative active site suggest possible mechanistic roles for Glu-244, Asp-154, His-122, His-45, and His-145.
The 2-A crystal structure of 6-oxo camphor hydrolase. New structural diversity in the crotonase superfamily.,Whittingham JL, Turkenburg JP, Verma CS, Walsh MA, Grogan G J Biol Chem. 2003 Jan 17;278(3):1744-50. Epub 2002 Nov 5. PMID:12421807[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Grogan G, Roberts GA, Bougioukou D, Turner NJ, Flitsch SL. The desymmetrization of bicyclic beta -diketones by an enzymatic retro-Claisen reaction. A new reaction of the crotonase superfamily. J Biol Chem. 2001 Apr 20;276(16):12565-72. PMID:11278926 doi:10.1074/jbc.M011538200
- ↑ Leonard PM, Grogan G. Structure of 6-oxo camphor hydrolase H122A mutant bound to its natural product, (2S,4S)-alpha-campholinic acid: mutant structure suggests an atypical mode of transition state binding for a crotonase homolog. J Biol Chem. 2004 Jul 23;279(30):31312-7. Epub 2004 May 11. PMID:15138275 doi:10.1074/jbc.M403514200
- ↑ Whittingham JL, Turkenburg JP, Verma CS, Walsh MA, Grogan G. The 2-A crystal structure of 6-oxo camphor hydrolase. New structural diversity in the crotonase superfamily. J Biol Chem. 2003 Jan 17;278(3):1744-50. Epub 2002 Nov 5. PMID:12421807 doi:10.1074/jbc.M211188200
