Shimada Hideaki, Tanigawa Takahiro, Matayoshi Kazunori, Katakura Kazufumi, Babazono Ken, Takayama Hiroyuki, Murahashi Tsuyoshi, Akita Hiroyuki, Higuchi Toshiyuki, Eto Masashi, Imamura Yorishige
Faculty of Education, Kumamoto University , Chuo-ku, Kumamoto , Japan .
J Enzyme Inhib Med Chem. 2014 Jun;29(3):397-400. doi: 10.3109/14756366.2013.790021. Epub 2013 May 8.
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.
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.
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.
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.
本研究旨在阐明烷基4-吡啶酮对四聚体羰基还原酶（TCBR）活性的比较抑制作用，并对其底物结合结构域进行表征。
在猪心脏的胞质部分检测烷基4-吡啶酮对TCBR催化的4-苯甲酰吡啶（4-BP）立体选择性还原的抑制作用。
在烷基4-吡啶酮中，具有五个碳原子直链烷基的4-己酰吡啶对TCBR活性的抑制作用最强，且为竞争性抑制剂。此外，用环己基取代己酮苯环上苯基的环己基戊基酮的还原能力比己酮低得多。
这些结果表明，除了对应于五个碳原子直链烷基的疏水裂缝外，TCBR的底物结合结构域中还存在一个对芳香基团有亲和力的疏水口袋。
