Recombinant Human ITPA, N-His

Introduction to Recombinant Human ITPA

Recombinant Human ITPA (Inosine Triphosphate Pyrophosphatase) is a protein that plays a crucial role in maintaining the balance of nucleotide pools in cells. It is a highly conserved enzyme found in all living organisms and is responsible for the hydrolysis of inosine triphosphate (ITP) into inosine monophosphate (IMP) and pyrophosphate (PPi). This process is essential for preventing the accumulation of ITP, which can be toxic to cells.

Structure of Recombinant Human ITPA

The structure of Recombinant Human ITPA consists of a single polypeptide chain of 199 amino acids with a molecular weight of approximately 23 kDa. It belongs to the HAM1 NTPase superfamily and has a conserved Nudix motif, which is essential for its enzymatic activity. The protein also contains a magnesium binding site, which is crucial for its catalytic function.

The crystal structure of Recombinant Human ITPA has been determined, revealing a homodimeric structure with each monomer consisting of two domains: the N-terminal domain, which contains the active site, and the C-terminal domain, which is involved in dimerization. The dimerization of ITPA is essential for its activity, as mutations in the dimerization interface can lead to a loss of function.

Activity of Recombinant Human ITPA

The main function of Recombinant Human ITPA is to maintain the balance of nucleotide pools in cells by hydrolyzing ITP into IMP and PPi. This process is essential for preventing the accumulation of ITP, which can be toxic to cells. ITPA also plays a role in DNA repair by removing ITP from the nucleotide pool, which can cause mutations during DNA replication.

Recombinant Human ITPA has a high specificity for ITP and can hydrolyze it at a rate of approximately 1000 molecules per minute. It also has low activity towards other nucleotide triphosphates, such as ATP, GTP, and UTP. The activity of ITPA is regulated by the concentration of magnesium ions, with higher levels of magnesium leading to increased activity. Mutations in the Nudix motif or magnesium binding site can lead to a loss of activity, which can result in the accumulation of ITP and DNA damage.

Application of Recombinant Human ITPA

Recombinant Human ITPA has various applications in both research and clinical settings. In research, it is used as a tool to study nucleotide metabolism and its role in DNA repair. Recombinant Human ITPA can also be used to screen for potential inhibitors or activators of the enzyme, which can have therapeutic implications.

In the clinic, Recombinant Human ITPA is used as a biomarker for certain diseases, such as inherited ITPA deficiency, which can lead to an accumulation of ITP and neurological symptoms. It is also being investigated as a potential therapeutic target for various diseases, including cancer, where ITPA inhibitors can sensitize cancer cells to chemotherapy.

In summary, Recombinant Human ITPA is a crucial enzyme that plays a vital role in maintaining the balance of nucleotide pools in cells. Its structure, activity, and application have been extensively studied, and it continues to be a valuable tool in both research and clinical settings. Further research on Recombinant Human ITPA may lead to a better understanding of nucleotide metabolism and potential therapeutic targets for various diseases.