2-hydroxy-dATP diphosphatase

2-hydroxy-dATP diphosphatase

MTH1 hydrolyzing oxidized nucleotide

MTH1 recognizing oxidized nucleotides

2-hydroxy-dATP diphosphatase, also known as MTH1, is an enzyme that plays a crucial role in maintaining the integrity of the nucleotide pool by hydrolyzing oxidized nucleotides. This enzyme is part of the nudix hydrolase family and is responsible for preventing the incorporation of damaged nucleotides into DNA, which can lead to mutations and genomic instability.

Function

The primary function of 2-hydroxy-dATP diphosphatase is to sanitize the nucleotide pool by hydrolyzing oxidized forms of deoxyribonucleoside triphosphates (dNTPs), such as 2-hydroxy-dATP. These oxidized nucleotides can arise from oxidative stress and, if incorporated into DNA, can cause transversion mutations. MTH1 specifically hydrolyzes these oxidized nucleotides to their corresponding monophosphates, thus preventing their incorporation into DNA.

Mechanism

MTH1 recognizes and binds to oxidized nucleotides through its active site, which is highly specific for damaged dNTPs. The enzyme catalyzes the hydrolysis of the pyrophosphate bond, converting the triphosphate form into a monophosphate and releasing inorganic pyrophosphate. This reaction is crucial for maintaining the fidelity of DNA replication and repair processes.

Biological significance

The activity of 2-hydroxy-dATP diphosphatase is essential for protecting cells from the deleterious effects of oxidative damage. By preventing the incorporation of oxidized nucleotides into DNA, MTH1 helps to maintain genomic stability and prevent mutations that could lead to cancer and other diseases. The enzyme is particularly important in cells exposed to high levels of oxidative stress, such as neurons and cancer cells.

Clinical relevance

Given its role in preventing DNA damage, MTH1 has been studied as a potential target for cancer therapy. Inhibitors of MTH1 have been developed with the aim of increasing the level of oxidative damage in cancer cells, thereby promoting cell death. However, the therapeutic potential of MTH1 inhibitors is still under investigation.

Related pages

• Nucleotide pool
• DNA repair
• Oxidative stress
• Mutagenesis

Gallery

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  MTH1 hydrolyzing oxidized nucleotide

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  MTH1 recognizing oxidized nucleotides

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  MTH1 Hydrolysis of Oxidized Nucleotide

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  MTH1 Recognition of Oxidized Nucleotides