6NF0

Nocturnin with bound NADPH substrate

6NF0 の概要

• エントリーDOI: 10.2210/pdb6nf0/pdb
• 分子名称: Nocturnin, CALCIUM ION, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (4 entities in total)
• 機能のキーワード: circadian clock, metabolism, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36275.60

構造登録者

Estrella, M.A.,Du, J.,Korennykh, A. (登録日: 2018-12-18, 公開日: 2019-05-01, 最終更新日: 2023-10-11)

主引用文献

Estrella, M.A.,Du, J.,Chen, L.,Rath, S.,Prangley, E.,Chitrakar, A.,Aoki, T.,Schedl, P.,Rabinowitz, J.,Korennykh, A.
The metabolites NADP+and NADPH are the targets of the circadian protein Nocturnin (Curled).
Nat Commun, 10:2367-2367, 2019

PubMed Abstract: Nocturnin (NOCT) is a rhythmically expressed protein that regulates metabolism under the control of circadian clock. It has been proposed that NOCT deadenylates and regulates metabolic enzyme mRNAs. However, in contrast to other deadenylases, purified NOCT lacks the deadenylase activity. To identify the substrate of NOCT, we conducted a mass spectrometry screen and report that NOCT specifically and directly converts the dinucleotide NADP into NAD and NADPH into NADH. Further, we demonstrate that the Drosophila NOCT ortholog, Curled, has the same enzymatic activity. We obtained the 2.7 Å crystal structure of the human NOCT•NADPH complex, which revealed that NOCT recognizes the chemically unique ribose-phosphate backbone of the metabolite, placing the 2'-terminal phosphate productively for removal. We provide evidence for NOCT targeting to mitochondria and propose that NADP(H) regulation, which takes place at least in part in mitochondria, establishes the molecular link between circadian clock and metabolism.

PubMed: 31147539
DOI: 10.1038/s41467-019-10125-z

実験手法

X-RAY DIFFRACTION (2.7 Å)