Comparative inhibition of tetrameric carbonyl reductase activity in pig heart cytosol by alkyl 4-pyridyl ketones
| Autor: | Yorishige Imamura, Hideaki Shimada, Kazunori Matayoshi, Hiroyuki Takayama, Ken Babazono, Toshiyuki Higuchi, Takahiro Tanigawa, Masashi Eto, Kazufumi Katakura, Hiroyuki Akita, Tsuyoshi Murahashi |
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| Rok vydání: | 2013 |
| Předmět: |
Ketone
Carbonyl Reductase Pyridines Swine Stereochemistry Aldo-Keto Reductases Substrate Specificity Catalysis Structure-Activity Relationship chemistry.chemical_compound Cytosol Non-competitive inhibition Aldehyde Reductase Drug Discovery Animals Phenyl group Alkyl Pharmacology chemistry.chemical_classification Binding Sites Tissue Extracts Chemistry Myocardium General Medicine Ketones Protein Structure Tertiary Stereoselectivity Protein Multimerization Hydrophobic and Hydrophilic Interactions Oxidation-Reduction Protein Binding |
| Zdroj: | Journal of Enzyme Inhibition and Medicinal Chemistry. 29:397-400 |
| ISSN: | 1475-6374 1475-6366 |
| Popis: | 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 th... |
| Databáze: | OpenAIRE |
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