Function
Nucleoside triphosphatase or nucleoside triphosphate diphosphohydrolase (NTPase) is responsible for degradation of nucleotides to their monophosphate form. NTPase is found in mammals and in pathogenic microbes. In mammals NTPase hs a crucial role in regulation of purinergic signalling by hydrolysis of extracellular nucleotides. The function of NTPase in pathogens is still unknown[1].
Relevance
The modulation of NTPase activity sems a good therapeutic method for regulating the concentration of ATP. High ATP concentration has been shown to be involved in various disorders in the CNS including brain injury, ischemia, neuro-inflammation, epilepsy, neuropathic pain and migraine[2].
Structural highlights
The 3D structure of the complex between NTPase 2 and the ATP analog AMPPNP shows the NTPase structure composed of two domains. Domain I contains the N-terminal and C-terminal and domain II the core residues. The structure contains 7 Cys-Cys bonds one of which located between domain I and II and reaching the diametrically positioned monomer was found by mutational analysis to be responsible for activation. The ATP analog - AMPPNP - is located in a cleft and forms interactions with domain I and domain II[3].
