Targeting TYMS for Cancer and Neurodegenerative Disorders (G7298)

Target Name: TYMS

NCBI ID: G7298

Targeting TYMS for Cancer and Neurodegenerative Disorders

TYMS, or Thymidylate Synthase Isoform 2, is a protein that plays a crucial role in the production of thymidylate, a key signaling molecule in various cellular processes. Mutations in the TYMS gene have been linked to a range of diseases, including cancer, neurodegenerative disorders, and autoimmune conditions. As a result, targeting TYMS has emerged as a promising strategy for the development of new treatments.

The protein encoded by the TYMS gene is a member of the superfamily of NAD+-dependent enzymes, known as the NAD+-dependent enzyme superfamily 1 (NAD+-ESF). These enzymes share a conserved catalytic core and are characterized by the presence of a nucleotide base (NAD+) and an electron transport chain (ETS). In the case of TYMS, the NAD+-dependent reaction involves the synthesis of thymidylate from its precursor, 2-thiouracil.

Thymidylate is a small molecule that plays a central role in various cellular processes, including DNA replication, transcription, and signaling pathways. It serves as a template for the DNA polymerase enzyme, which uses the template to synthesize new DNA strands. Additionally, thymidylate is involved in the regulation of various cellular processes, including cell growth, apoptosis, and inflammation.

The TYMS enzyme is involved in the synthesis of thymidylate from its precursor, 2-thiouracil. The reaction starts with 2-thiouracil, which is converted to thymidylate through a series of intermediate steps. The first step in the conversion is the addition of a phosphate group to the carbonyl group (C=O) of 2-thiouracil. This reaction is catalyzed by the NAD+-dependent enzyme Pyruvate Carrier Reductase (PCR), which is part of the TCA cycle.

The second step in the conversion of 2-thiouracil to thymidylate involves the addition of a second phosphate group to the carbonyl group of 2-thiouracil. This reaction is catalyzed by TYMS, which is a NAD+-dependent enzyme that uses ATP as a source of energy. The TYMS enzyme is responsible for catalyzing the transfer of the phosphate group from ATP to the carbonyl group of 2-thiouracil.

The role of TYMS in the synthesis of thymidylate has important implications for the development of new treatments. If TYMS is targeted by a drug, it can disrupt the normal function of this enzyme and lead to the production of abnormally high levels of thymidylate. This can lead to a range of potential side effects, including nausea, vomiting, and muscle weakness.

In addition to its role in the synthesis of thymidylate, TYMS is also involved in the regulation of various cellular processes. For example, TYMS has been shown to play a role in the regulation of cell growth and apoptosis. Mutations in the TYMS gene have been linked to the development of various neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease.

Targeting TYMS as a drug target has the potential to treat a range of diseases. For example, TYMS has been shown to be involved in the development of cancer, and inhibiting its function may be a promising strategy for the treatment of cancer. Additionally, TYMS has been linked to the development of autoimmune conditions, and inhibiting its function may be a strategy for the treatment of these conditions.

In conclusion, TYMS is a protein that plays a crucial role in the production of thymidylate, a key signaling molecule in various cellular processes. Mutations in the TYMS gene have been linked to a range of diseases, including cancer, neurodegenerative disorders, and autoimmune conditions. As a result, targeting TYMS has emerged as a promising strategy for

Protein Name: Thymidylate Synthetase

Functions: Catalyzes the reductive methylation of 2'-deoxyuridine 5'-monophosphate (dUMP) to thymidine 5'-monophosphate (dTMP), using the cosubstrate, 5,10- methylenetetrahydrofolate (CH2H4folate) as a 1-carbon donor and reductant and contributes to the de novo mitochondrial thymidylate biosynthesis pathway

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