nuc_hydro: Nucleoside hydrolases. Nucleoside hydrolases cleave the N-glycosidic bond in nucleosides generating ribose and the respective base. These enzymes vary in their substrate specificity. This group contains eukaryotic, bacterial and archeal proteins similar to the inosine-uridine preferring nucleoside hydrolase from Crithidia fasciculata, the xanthosine-inosine-uridine-adenosine-preferring nucleoside hydrolase RihC from Salmonella enterica serovar Typhimurium, the purine-specific inosine-adenosine-guanosine-preferring nucleoside hydrolase from Trypanosoma vivax and, pyrimidine-specific uridine-cytidine preferring nucleoside hydrolases such as URH1 from Saccharomyces cerevisiae, RihA and RihB from Escherichia coli. Nucleoside hydrolases are of interest as a target for antiprotozoan drugs as, no nucleoside hydrolase activity or genes encoding these enzymes have been detected in humans and, parasitic protozoans lack de novo purine synthesis relying on nucleoside hydrolase to scavenge purine and/or pyrimidines from the environment.
Structure:1HP0_A, Trypanosoma vivax, an inosine-adenosine-guanosine-preferring nucleoside hydrolase, bound with 3-deaza-adenosine, Ca2+ cofactor contacts at 3.5A
Comment:Most nucleoside hydrolases possess either a tryptophan or a histidine at a position equivalent to PDB H241 in the base-aspecific nucleoside hydrolase of Crithidia fasciculate (2MAS_A). This histidine has been identified as the general acid in the catalysis. In the nucleoside hydrolase of the parasite Trypanosoma vivax (1HP0_A), as an alternative to general acid catalysis, the purine base of the substrate is bound between the aromatic side chains of W83 and W260, promoting the protonation of the purine base at N-7.
Structure:1EZR_A: Leishmania major, inosine-uridine preferring nucleoside hydrolase showing calcium bound at the active site, contacts at 3.5A.
Jiyao W et al.(2023). "The conserved domain database in 2023.",