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J Enzyme Inhib Med Chem. 2014 Jun;29(3):397-400. doi: 10.3109/14756366.2013.790021. Epub 2013 May 8.

Comparative inhibition of tetrameric carbonyl reductase activity in pig heart cytosol by alkyl 4-pyridyl ketones.

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1
Faculty of Education, Kumamoto University , Chuo-ku, Kumamoto , Japan .

Abstract

CONTEXT AND OBJECTIVE:

The present study is to elucidate the comparative inhibition of tetrameric carbonyl reductase (TCBR) activity by alkyl 4-pyridyl ketones, and to characterize its substrate-binding domain.

MATERIALS AND METHODS:

The inhibitory effects of alkyl 4-pyridyl ketones on the stereoselective reduction of 4-benzoylpyridine (4-BP) catalyzed by TCBR were examined in the cytosolic fraction of pig heart.

RESULTS:

Of alkyl 4-pyridyl ketones, 4-hexanoylpyridine, which has a straight-chain alkyl group of five carbon atoms, inhibited most potently TCBR activity and was a competitive inhibitor. Furthermore, cyclohexyl pentyl ketone, which is substituted by cyclohexyl group instead of phenyl group of hexanophenone, had much lower ability to be reduced than hexanophenone.

DISCUSSION AND CONCLUSION:

These results suggest that in addition to a hydrophobic cleft corresponding to a straight-chain alkyl group of five carbon atoms, a hydrophobic pocket with affinity for an aromatic group is located in the substrate-binding domain of TCBR.

KEYWORDS:

4-Benzoylpyridine; 4-hexanoylpyridine; competitive inhibition; cyclohexyl pentyl ketone; stereoselective reduction

PMID:
23656552
DOI:
10.3109/14756366.2013.790021
[Indexed for MEDLINE]
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