| FunctionNucleoside 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].
RelevanceThe 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 highlightsToxoplasma gondii NTPase 2 is dimer of dimers (PDB code 4a5a). 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].
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3D structures of nucleoside triphosphatase3D structures of nucleoside triphosphatase
Updated on 17-August-2023
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- Nucleoside triphosphatase 1
- 4a57 - TgNTPase 1 - Toxoplasma gondii
- 4a59 - TgNTPase 1 + AMP
- Nucleoside triphosphatase 2
- 4jep - TgNTPase 2
- 4a5b - TgNTPase 2 (mutant)
- 4kh4, 4a5a - TgNTPase 2 (mutant) + AMPPNP
- 4kh5, 4kh6 - TgNTPase 2 (mutant) + AMPNP
- Nucleoside triphosphatase Nudi
- 6dt3 - Nudi - Klebsiella pneumoniae
- 3oga, 3n77 - Nudi - Salmonella enterica
- Nucleoside triphosphatase cancer-related
- 2i3b - NTPase - human- NMR
- Nucleoside triphosphatase
- 3s86 - NTPase - Thermotoga maritima
- 3agr - NTPase - Neospora caninum
- 7aoh - NTPase I in transcribing complex - Vaccinia virus – Cryo EM
ReferencesReferences
- ↑ Krug U, Totzauer R, Zebisch M, Strater N. The ATP/ADP Substrate Specificity Switch between Toxoplasma gondii NTPDase1 and NTPDase3 is Caused by an Altered Mode of Binding of the Substrate Base. Chembiochem. 2013 Oct 2. doi: 10.1002/cbic.201300441. PMID:24115522 doi:http://dx.doi.org/10.1002/cbic.201300441
- ↑ Roszek K, Czarnecka J. Is Ecto-nucleoside Triphosphate Diphosphohydrolase (NTPDase)-based Therapy of Central Nervous System Disorders Possible? Mini Rev Med Chem. 2015;15(1):5-20. doi: 10.2174/1389557515666150219114416. PMID:25694082 doi:http://dx.doi.org/10.2174/1389557515666150219114416
- ↑ Krug U, Zebisch M, Krauss M, Strater N. Structural insight into the activation mechanism of Toxoplasma gondii nucleoside triphosphate diphosphohydrolases by disulfide reduction. J Biol Chem. 2011 Nov 30. PMID:22130673 doi:10.1074/jbc.M111.294348