ID 112024
著者
加藤, 有介 Tokyo University of Pharmacy and Life Sciences|Himeji Hinomoto College|Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
Kihara, Hiroshi Himeji Hinomoto College
小島, 正樹 Tokyo University of Pharmacy and Life Sciences
キーワード
Sirtuin
Metabolism
Homology modeling
Cancer
Docking
Ischemic heart disease
資料タイプ
学術雑誌論文
抄録
Sirtuin4 (Sirt4) is one of the mammalian homologues of Silent information regulator 2 (Sir2), which promotes the longevity of yeast, C. elegans, fruit flies and mice. Sirt4 is localized in the mitochondria, where it contributes to preventing the development of cancers and ischemic heart disease through regulating energy metabolism. The ADP-ribosylation of glutamate dehydrogenase (GDH), which is catalyzed by Sirt4, downregulates the TCA cycle. However, this reaction mechanism is obscure, because the structure of Sirt4 is unknown. We here constructed structural models of Sirt4 by homology modeling and threading, and docked nicotinamide adenine dinucleotide+ (NAD+) to Sirt4. In addition, a partial GDH structure was docked to the Sirt4-NAD+ complex model. In the ternary complex model of Sirt4-NAD+-GDH, the acetylated lysine 171 of GDH is located close to NAD+. This suggests a possible mechanism underlying the ADP-ribosylation at cysteine 172, which may occur through a transient intermediate with ADP-ribosylation at the acetylated lysine 171. These results may be useful in designing drugs for the treatment of cancers and ischemic heart disease.
掲載誌名
Computational Biology and Chemistry
ISSN
14769271
cat書誌ID
AA11947228
AA11829786
出版者
Elsevier
74
開始ページ
94
終了ページ
104
発行日
2018-03-10
備考
論文本文は2020-03-10以降公開予定
権利情報
© 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
EDB ID
出版社版DOI
出版社版URL
言語
eng
著者版フラグ
その他
部局
先端酵素学研究所