6NF0

Nocturnin with bound NADPH substrate

Summary for 6NF0

• Entry DOI: 10.2210/pdb6nf0/pdb
• Descriptor: Nocturnin, CALCIUM ION, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (4 entities in total)
• Functional Keywords: circadian clock, metabolism, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 36275.60

Authors

Estrella, M.A.,Du, J.,Korennykh, A. (deposition date: 2018-12-18, release date: 2019-05-01, Last modification date: 2023-10-11)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.7 Å)