NNMT Antibodies

Structure of NNMT

NNMT is an enzyme protein with a molecular weight of approximately 29 kDa. Its weight varies slightly among different mammals, mainly due to the differences in amino acid sequences between species.

This enzyme is composed of approximately 264 amino acids and exhibits a classic methyltransferase folding conformation. The core of its three-dimensional structure is a typical seven-stranded β-sheet, surrounded by multiple α-helices, which together form the binding pocket for S-adenosylmethionine (SAM) and nicotinamide (NAM). Several key amino acid residues in the catalytic active center (such as Asp-197 and Tyr-20 in the human NNMT) are crucial for substrate recognition and the methyltransfer reaction, determining its specificity for nicotinamide. This structural feature enables NNMT to precisely regulate the metabolic flow of nicotinamide within the cell and affect the biosynthesis of NAD+.

Fig. 1 The NNMT–DNMT1 Axis and Sensitivity to OXPHOS Inhibition.¹

Key structural properties of NNMT:

• Classical methyltransferase fold structure with a seven-stranded β-fold at the core
• Hydrophilic catalytic pocket, used for binding S-adenosylmethionine (SAM) and nicotinamide
• Key catalytic residues (such as aspartic acid and tyrosine) precisely regulate methyl transfer reactions
• Flexible ring area in the substrate recognition and product release

Functions of NNMT

The main function of the NNMT gene is to catalyze the N-methylation reaction of nicotinamide. However, it is also widely involved in various physiological and pathological processes such as energy metabolism, epigenetic regulation, and cell signal transduction.

Unlike enzymes that typically exhibit saturated kinetics, the activity of NNMT is highly dependent on the local concentrations of the substrates nicotinamide and SAM. Its expression levels vary significantly in different tissues and metabolic states, highlighting its dynamic regulatory role in connecting the cellular metabolic state with functional output.

Applications of NNMT and NNMT Antibody in Literature

1. Wu, Changqing, et al. "NNMT‐DNMT1 axis is essential for maintaining cancer cell sensitivity to oxidative phosphorylation inhibition." Advanced Science 10.1 (2023): 2202642. https://doi.org/10.1002/advs.202202642

The article indicates that the NNMT-DNMT1 axis regulates the sensitivity of cancer cells to OXPHOS inhibition. Cancer cells with low NNMT and high DNMT1 expression rely on OXPHOS and are sensitive to inhibitors (such as berberine); high NNMT leads to drug resistance. Clinical data confirm that this expression pattern can predict the treatment response of colorectal adenomas and provide a biomarker for targeted therapy.

2. Ma, Yilei, et al. "NNMT/1‐MNA Promote Cell‐Cycle Progression of Breast Cancer by Targeting UBC12/Cullin‐1‐Mediated Degradation of P27 Proteins." Advanced Science 11.9 (2024): 2305907. https://doi.org/10.1002/advs.202305907

The study found that NNMT is highly expressed in breast cancer and produces the metabolite 1-MNA. This metabolite enhances cullin-1 neddylation, thereby promoting the degradation of the p27 protein, and subsequently driving the cell cycle progression and tumor progression. This reveals the crucial role of NNMT/1-MNA in the remodeling of the tumor microenvironment.

3. Huang, Qi, et al. "Multi-omics analysis reveals NNMT as a master metabolic regulator of metastasis in esophageal squamous cell carcinoma." NPJ precision oncology 8.1 (2024): 24. https://doi.org/10.1038/s41698-024-00509-w

This study, through metabolomics analysis, discovered that in patients with esophageal squamous cell carcinoma (ESCC) with lymph node metastasis (LN+), the metabolite MNA significantly increased in both the tumor and plasma. This increase originated from the overexpression of NNMT. NNMT inhibits the expression of E-cadherin through consuming the methyl donor SAM, thereby reducing the epigenetic levels (lowering H3K4me3 and m6A modifications) and suppressing EMT and metastasis. It can also serve as a detection marker for LN+.

4. Yang, Qingfan, et al. "PI (4, 5) P2 alleviates colitis by inhibiting intestinal epithelial cell pyroptosis through NNMT-mediated RBP4 m6A modification." Cell Death & Disease 15.12 (2024): 923. https://doi.org/10.1038/s41419-024-07276-3

The study found that PI(4,5)P2 can upregulate NNMT, reduce the stability of RBP4 mRNA through m6A modification, thereby inhibiting pyroptosis of intestinal epithelial cells and alleviating colonic inflammation in Crohn's disease. This suggests that the PI(4,5)P2/NNMT pathway is a potential therapeutic target.

5. Türkmen, Osman, et al. "NNMT overexpression is an adverse prognostic factor in uterine leiomyosarcoma." Turkish Journal of Medical Sciences 54.4 (2024): 804-810. https://doi.org/10.55730/1300-0144.5852

This study is the first to reveal that NNMT is significantly overexpressed in uterine sarcoma, and its expression level is positively correlated with tumor stage and recurrence risk. It can serve as a potential marker for differentiating sarcoma from benign myoma and provides a new target for the treatment of mesenchymal tumors.

Creative Biolabs: NNMT Antibodies for Research

Creative Biolabs specializes in the production of high-quality NNMT antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

• Custom NNMT Antibody Development: Tailor-made solutions to meet specific research requirements.
• Bulk Production: Large-scale antibody manufacturing for industry partners.
• Technical Support: Expert consultation for protocol optimization and troubleshooting.
• Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our NNMT antibodies, custom preparations, or technical support, contact us at email.