Bis(5'-adenosyl)-triphosphatase

  [[File:|frameless|alt=]]

Identifiers
EC number	3.6.1.29
CAS number	9027-73-0
Alt. names
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway

Bis(5'-adenosyl)-triphosphatase is an enzyme that catalyzes the hydrolysis of P1,P4-bis(5'-adenosyl) tetraphosphate (Ap4A) to yield two molecules of adenosine monophosphate (AMP). This enzyme plays a crucial role in the regulation of intracellular levels of Ap4A, a molecule involved in various cellular processes.

Structure

Bis(5'-adenosyl)-triphosphatase is a member of the nudix hydrolase family, characterized by the presence of a conserved nudix box motif. This motif is essential for the enzyme's catalytic activity, as it coordinates the binding of a divalent cation, typically magnesium or manganese, which is necessary for the hydrolysis reaction.

Function

The primary function of bis(5'-adenosyl)-triphosphatase is to regulate the concentration of Ap4A within the cell. Ap4A is a diadenosine polyphosphate that acts as a signaling molecule, influencing various cellular processes such as DNA replication, protein synthesis, and cell cycle progression. By hydrolyzing Ap4A to AMP, bis(5'-adenosyl)-triphosphatase modulates these processes and maintains cellular homeostasis.

Mechanism

The enzymatic reaction catalyzed by bis(5'-adenosyl)-triphosphatase involves the cleavage of the phosphoanhydride bond in Ap4A. The reaction proceeds as follows:

Ap4A + H2O → 2 AMP

The enzyme binds to Ap4A and a water molecule, facilitating the nucleophilic attack on the phosphoanhydride bond. The presence of a divalent cation is crucial for stabilizing the transition state and enhancing the reaction rate.

Biological Significance

Bis(5'-adenosyl)-triphosphatase is involved in the regulation of cellular stress responses. Under conditions of oxidative stress or heat shock, the levels of Ap4A can increase, leading to alterations in cellular signaling pathways. By hydrolyzing Ap4A, bis(5'-adenosyl)-triphosphatase helps to restore normal cellular function and prevent the deleterious effects of prolonged stress.

Clinical Implications

Alterations in the activity of bis(5'-adenosyl)-triphosphatase have been implicated in various diseases. For instance, dysregulation of Ap4A metabolism has been associated with cancer, where abnormal levels of Ap4A can affect cell proliferation and apoptosis. Understanding the role of bis(5'-adenosyl)-triphosphatase in these processes may provide insights into potential therapeutic targets.

Research Directions

Current research on bis(5'-adenosyl)-triphosphatase focuses on elucidating its structure-function relationships, identifying its role in different cellular contexts, and exploring its potential as a biomarker for disease. Advances in structural biology and biochemistry are expected to shed light on the detailed mechanisms of this enzyme and its interactions with other cellular components.

See Also

• Nudix hydrolase
• Diadenosine polyphosphate
• Adenosine monophosphate

External Links

• [Enzyme Database Entry]
• [Protein Data Bank]