title: Comparative inhibition of tetrameric carbonyl reductase activity in pig heart cytosol by alkyl 4-pyridyl ketones.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Faculty of Education, Kumamoto University , Chuo-ku, Kumamoto , Japan .
authors: Hideaki
authors: H
authors: Shimada
authors: Takahiro
authors: T
authors: Tanigawa
authors: Kazunori
authors: K
authors: Matayoshi
authors: Kazufumi
authors: K
authors: Katakura
authors: Ken
authors: K
authors: Babazono
authors: Hiroyuki
authors: H
authors: Takayama
authors: Tsuyoshi
authors: T
authors: Murahashi
authors: Hiroyuki
authors: H
authors: Akita
authors: Toshiyuki
authors: T
authors: Higuchi
authors: Masashi
authors: M
authors: Eto
authors: Yorishige
authors: Y
authors: Imamura
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000074408:Aldo-Keto Reductases; D000818:Animals; D001665:Binding Sites; D003600:Cytosol / Q000737:chemistry / Q000201:enzymology*; D057927:Hydrophobic and Hydrophilic Interactions; D007659:Ketones / Q000737:chemistry*; D009206:Myocardium / Q000201:enzymology*; D010084:Oxidation-Reduction; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D011725:Pyridines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013552:Swine; D014020:Tissue Extracts / Q000737:chemistry
chemical_list: D007659:Ketones; D011725:Pyridines; D014020:Tissue Extracts; C066738:4-benzoylpyridine; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase
keywords: 4-Benzoylpyridine; 4-hexanoylpyridine; competitive inhibition; cyclohexyl pentyl ketone; stereoselective reduction