Nucleoside hydrolase (NH)

Nucleoside hydrolase (NH) is a calcium-dependent metalloenzyme that catalyzes the hydrolysis of the N-glycosidic bond in ribonucleosides, releasing a free nitrogenous base and a ribose sugar. This enzyme is essential for the survival of many protozoan parasites, such as Leishmania, Trypanosoma, and Trichomonas, which are auxotrophic for purines and must rely on salvage pathways to obtain the precursors for DNA and RNA synthesis. Notably, NH is absent in humans and other mammals, who instead utilize nucleoside phosphorylases for the same metabolic function, providing a high degree of target selectivity for drug development. Therapeutic strategies targeting NH focus on transition-state analogs, such as Immucillins, which mimic the oxocarbenium-ion character of the catalytic reaction to achieve high-affinity binding. By inhibiting this enzyme, these compounds effectively starve the parasite of essential nucleobases, leading to growth arrest and death while sparing the host's metabolic machinery.

Other names

Nucleoside ribohydrolaseRibonucleoside hydrolaseN-ribohydrolaseInosine-uridine nucleoside hydrolase (IU-NH)Inosine-adenosine-guanosine nucleoside hydrolase (IAG-NH)Inosine-guanosine nucleoside hydrolase (IG-NH)

Competitive inhibition of the N-glycosidic bond hydrolysis by mimicking the oxocarbenium ion transition state, thereby blocking the salvage of essential purines and pyrimidines.