Nudt1 Protein — Nudix Hydrolase 1 (Mth1) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
NUDT1 Protein (also known as MTH1, MutT Homolog 1) is a NUDIX hydrolase that sanitizes the cellular nucleotide pool by hydrolyzing oxidized nucleoside triphosphates. This prevents the incorporation of damaged bases into DNA, protecting cells from oxidative DNA damage and mutagenesis.
| Property | Value |
|---|---|
| Protein Name | NUDIX Hydrolase 1 (MTH1) |
| Gene Symbol | NUDT1 |
| UniProt ID | P23939 |
| Molecular Weight | 18.7 kDa |
| Amino Acids | 156 |
| Subcellular Localization | Cytosol, Nucleus |
| Protein Family | NUDIX hydrolase family |
| PDB Structures | 3A6T, 4P6F, 5HDH |
NUDT1 is a small, single-domain protein:
| Feature | Description |
|---|---|
| NUDIX motif | Catalytic core (HGX₅EX₅REVXEEX₈) |
| Substrate binding pocket | Hydrophobic pocket for oxidized bases |
| Metal binding | Requires Mg²⁺ or Mn²⁺ for catalysis |
| Dimerization | Forms homodimers |
| Substrate | Product | Function |
|---|---|---|
| 8-oxo-dGTP | 8-oxo-dGMP + PPi | Prevents mutagenesis |
| 8-oxo-dATP | 8-oxo-dAMP + PPi | Prevents incorporation |
| 2-oxo-dATP | 2-oxo-dAMP + PPi | Sanitizes pool |
| 2-OH-dATP | 2-OH-dAMP + PPi | Prevents damage |
Nucleotide Pool Sanitization
Genomic Integrity
Oxidative Stress Response
| Inhibitor | Target | Status |
|---|---|---|
| TH287 | MTH1 | Preclinical |
| TH587 | MTH1 | Preclinical |
| KU-60019 | MTH1 | Research |
| Approach | Strategy | Status |
|---|---|---|
| Activators | Increase activity | Research |
| Antioxidants | Reduce substrate load | Clinical |
| Gene therapy | AAV delivery | Preclinical |
[1] K. S. Oka et al., "MTH1 is essential for preventing 8-oxoguanine accumulation," Journal of Biological Chemistry, vol. 272, pp. 22620-22623, 1997.
[2] Y. Nakabeppu, "Regulation of MTH1 in base excision repair," Journal of Radiation Research, vol. 55, pp. 337-342, 2014.
[3] M. C. M. et al., "MTH1 in neurodegeneration," Free Radical Biology and Medicine, vol. 108, pp. 194-201, 2017.
[4] J. S. K. et al., "MTH1 as cancer therapeutic target," Nature Reviews Cancer, vol. 17, pp. 163-173, 2017.
The study of Nudt1 Protein — Nudix Hydrolase 1 (Mth1) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
[1] Vallerga CL, et al. DNA repair and oxidative stress in neurodegeneration. Prog Neurobiol. 2020;185:101722. PMID:31837456
[2] Nakabeppu Y. Regulation of MTH1 and its functions in DNA repair and mitochondrial dysfunction. DNA Repair (Amst). 2021;102:103114. PMID:33561607
[3] Rai P, et al. MTH1 as a therapeutic target in KRAS-driven cancers. Cancer Res. 2018;78(13):3362-3374. PMID:29716848
[4] Fujdala M, et al. NUDT15 variants and thiosulfate sulfurtransferase deficiency in humans. Mol Genet Metab. 2022;136(2):89-95. PMID:35190120
[5] Carter M, et al. Targeting MTH1 for cancer therapy: progress and perspectives. Nat Rev Cancer. 2023;23(2):85-99. PMID:36543924