NUDT1 Human

Nudix Type Motif 1 Human Recombinant
Shipped with Ice Packs
In Stock

Description

DNA/RNA Sanitization

NUDT1 prevents the misincorporation of oxidized nucleotides during replication and transcription, thereby mitigating oxidative DNA damage (ODD) . This is critical in:

  • Cancer cells: High NUDT1 expression counteracts MYC-driven reactive oxygen species (ROS) production, enabling survival under oxidative stress .

  • Aging: Overexpression in mice reduces 8-oxoguanine levels in DNA, correlating with a 16% lifespan extension .

Regulation and Activity

  • MYC-PLK1 Axis: MYC overexpression induces PLK1-mediated phosphorylation of NUDT1, enhancing its enzymatic activity without altering protein levels .

  • FOXM1 Dependency: In pulmonary arterial hypertension (PAH), FOXM1 upregulates NUDT1 to protect against oxidative damage .

Cancer

NUDT1 is overexpressed in aggressive cancers, including:

Cancer TypeExpression PatternClinical Relevance
B-cell lymphomaElevated in Burkitt’s lymphoma, DLBCL, FL Potential therapeutic target
Renal cell carcinomaCorrelates with poor prognosis and immune infiltration (Tregs, CD8+ T cells) Independent prognostic marker (HR=1.437)
Colorectal cancerAssociated with 8-oxo-dGTP accumulation Biomarker for disease progression

Aging and Neurodegeneration

NUDT1-null mice exhibit elevated 8-oxo-dGTP and accelerated aging, while overexpression delays oxidative damage accumulation .

Inhibitors and Mechanisms

CompoundMechanismPreclinical Efficacy
TH588Competitive inhibition of NUDT1Cytotoxicity in MYC-driven cancers
(S)-CrizotinibSelective NUDT1 inhibitionReverses PAH vascular remodeling
KaronudibNUDT1 suppressionAnti-tumor effects in B-cell lymphoma

Controversies: Early inhibitors like TH588 showed promise, but later studies (e.g., AstraZeneca, MD Anderson) reported limited efficacy, questioning NUDT1’s validity as a target .

Prognostic and Diagnostic Value

NUDT1 serves as a biomarker in:

  • Renal cell carcinoma: High expression correlates with reduced survival (PFS/OS) and immune checkpoint upregulation (PD-1, LAG3) .

  • Lymphoma: Elevated mRNA in germinal center B cells and aggressive subtypes .

Product Specs

Introduction
NUDT1, an enzyme, plays a crucial role in maintaining the integrity of DNA and RNA by hydrolyzing oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP. This action prevents the misincorporation of these damaged nucleotides, particularly 8-oxo-dGTP, into DNA, thus mitigating the risk of A:T to C:G transversions. Primarily located in the cytoplasm, with a presence also in mitochondria, NUDT1 is essential for the sanitization of nucleotide pools in both cellular compartments. The enzyme's activity is particularly vital in rapidly dividing cells, where its expression is markedly higher compared to resting cells, reflecting its role in safeguarding against mutations during replication and transcription. Such mutations, if left unchecked, can contribute to severe conditions like carcinogenesis and neurodegeneration.
Description
Recombinant human NUDT1, with a 20 amino acid His tag at the N-terminus, is produced in E. coli. This purified protein is a single, non-glycosylated polypeptide chain comprising 176 amino acids (with 156 a.a. from NUDT1) and has a molecular weight of 20.1kDa. The purification process employs proprietary chromatographic techniques.
Physical Appearance
A clear, colorless solution that has been sterilized by filtration.
Formulation
NUDT1 is supplied as a 1 mg/ml solution in a buffer consisting of 20mM Tris-HCl (pH 8.0), 10% glycerol, 2mM DTT, and 100mM NaCl.
Stability
For short-term storage (2-4 weeks), keep at 4°C. For extended storage, freeze at -20°C. Adding a carrier protein like HSA or BSA (0.1%) is recommended for long-term storage. Avoid repeated freeze-thaw cycles.
Purity
Purity exceeds 95.0% as assessed by SDS-PAGE.
Synonyms
7,8-dihydro-8-oxoguanine triphosphatase, 8-oxo-dGTPase, Nucleoside diphosphate-linked moiety X motif 1, Nudix motif 1, NUDT1, MTH1.
Source
Escherichia Coli.
Amino Acid Sequence

MGSSHHHHHH SSGLVPRGSH MGASRLYTLV LVLQPQRVLL GMKKRGFGAG RWNGFGGKVQ EGETIEDGAR RELQEESGLT VDALHKVGQI VFEFVGEPEL MDVHVFCTDS IQGTPVESDE MRPCWFQLDQ IPFKDMWPDD SYWFPLLLQK KKFHGYFKFQ GQDTILDYTL REVDTV.

Product Science Overview

Function and Importance

NUDT1 hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP and 8-oxo-dATP, into their corresponding monophosphates. This activity prevents the incorporation of these oxidized nucleotides into DNA, which could otherwise lead to mutations and genomic instability . The enzyme is predominantly found in the cytoplasm, with some presence in the mitochondria, indicating its role in sanitizing nucleotide pools for both nuclear and mitochondrial genomes .

Expression and Localization

NUDT1 is expressed at higher levels in proliferating cells compared to resting cells, highlighting its importance in rapidly dividing tissues. This differential expression suggests that NUDT1 is particularly crucial in preventing mutagenesis during DNA replication and transcription .

Structural Characteristics

The human recombinant form of NUDT1 is typically produced in Escherichia coli and is a single, non-glycosylated polypeptide chain containing 176 amino acids. It is often fused with a 20 amino acid His tag at the N-terminus to facilitate purification . The enzyme has a molecular mass of approximately 20.1 kDa .

Industrial Production and Purification

The recombinant NUDT1 is purified using proprietary chromatographic techniques to achieve a purity greater than 95%, as determined by SDS-PAGE . The enzyme is formulated in a solution containing Tris-HCl buffer, glycerol, dithiothreitol (DTT), and sodium chloride (NaCl) to ensure stability and activity .

Applications and Research

NUDT1 is widely used in laboratory research to study its role in DNA repair and mutagenesis. Its ability to hydrolyze oxidized nucleotides makes it a valuable tool for understanding the mechanisms of genomic maintenance and the prevention of diseases such as cancer and neurodegeneration .

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