The Molecular Mechanisms Underlying the Interaction Between NAD+/NMN and DBC1

The Molecular Mechanisms Underlying the Interaction Between NAD+/NMN and DBC1


Oxidized form of nicotinamide adenine dinucleotide (NAD+) and its precursor nicotinamide mononucleotide (NMN) have been uncovered to restore DNA repair and prevent cancer progression via the deleted in breast cancer 1 (DBC1). This research is committed to deciphering the detailed molecular mechanisms.

About DBC1

DBC1 is a nuclear protein initially cloned from a human chromosome 8p21 region, which can modulate diversified targets by protein-protein interaction, contributing to various cellular processes such as apoptosis, DNA repair, senescence, transcription, metabolism, circadian cycle, epigenetic regulation, cell proliferation, and tumorigenesis.

The affinity and molecular binding mechanisms between NAD+/NMN and DBC1354–396

Under the help of nuclear magnetic resonance (NMR) and Isothermal titration calorimetry (ITC) experiments, it is verified that both NAD+ and NMN have a binding relationship with the NHD domain of DBC1. Specifically, NAD+ interacts with DBC1354-396 through hydrogen bonds, with a binding affinity (8.99 μM) nearly twice that of NMN (17.0 μM) and the key binding sites are primarily residues E363 and D372.

The vital roles of E363 and D372 mutagenesis in ligand-protein interaction

The N-terminal loop of DBC1354-396 encloses the small ligand within a local space, anchoring NAD+ and NMN to the protein through key amino acid residues E363 and D372 via hydrogen bonding.


Both NAD+ and its precursor NMN can bind to DBC1's NHD domain (DBC1354–396) at key sites E363 and D372, providing novel clues for the development of targeted therapies and drug research on DBC1-associated disease including tumors.


Ou L, Zhao X, Wu IJ, et al. Molecular mechanism of NAD+ and NMN binding to the Nudix homology domains of DBC1. Int J Biol Macromol. Published online February 12, 2024. doi:10.1016/j.ijbiomac.2024.130131


BONTAC has been dedicated to the R&D, manufacture and sale of raw materials for coenzyme and natural products since 2012, with self-owned factories, over 170 global patents as well as strong R&D team consisting of Doctors and Masters. BONTAC has rich R&D experience and advanced technology in the biosynthesis of NAD and its precursors (eg. NMN), with various forms to be selected (eg. endoxin-free IVD-grade NAD, Na-free or Na-containing NAD; NR-CL or NR-Malate). High quality and stable supply of products can be better ensured here with the exclusive Bonpure seven-step purification technology and Bonzyme Whole-enzymatic method.


This article is based on the reference in the academic journal. The relevant information is provided for sharing and learning purposes only, and does not represent any medical advice purposes. If there is any infringement, please contact the author for deletion. The views expressed in this article do not represent the position of BONTAC.

Under no circumstances will BONTAC be held responsible or liable in any way for any claims, damages, losses, expenses, costs or liabilities whatsoever (including, without limitation, any direct or indirect damages for loss of profits, business interruption or loss of information) resulting or arising directly or indirectly from your reliance on the information and material on this website.


Get In Touch

Recommend Read

Leave Your Message