nuc_hydro_ TvIAG: Nucleoside hydrolases similar to the Inosine-adenosine-guanosine-preferring nucleoside hydrolase from Trypanosoma vivax. Nucleoside hydrolases cleave the N-glycosidic bond in nucleosides generating ribose and the respective base. Nucleoside hydrolases vary in their substrate specificity. This group contains eukaryotic and bacterial proteins similar to the purine specific inosine-adenosine-guanosine-preferring nucleoside hydrolase (IAG-NH) from T. vivax. T. vivax IAG-NH is of the order of a thousand to ten thousand fold more specific towards the naturally occurring purine nucleosides, than towards the pyrimidine nucleosides.
Structure:1HP0_A, Trypanosoma vivax, inosine-adenosine-guanosine- preferring nucleoside hydrolase, bound with 3-deaza-adenosine contacts at 3.5A. Note the Ca2+ cofactor bound at the bottom of the active site.
Comment:Trypanosoma vivax, inosine-adenosine-guanosine- preferring nucleoside hydrolase (IAG-NH) is a homodimer
Comment:The T. vivax dimer contains two active sites. Kinetic studies show no co-operativty between the two sites supporting that they act independently.
Comment:1HP0, PDB D10 is the proposed general base, abstracting a proton from a nucelophilic water molecule
Comment:In inosine-adenosine-guanosine- preferring nucleoside hydrolase from Trypanosoma vivax (1HP0_A), the purine base is stacked nearly parallel between two tryptophans: (PDB W83 and PDB W260). This stacking sandwich is believed to promote the protonation of the purine base at N-7. It is not present in the inosine-uridine-preferring nucleoside hydrolases which use histidine (at a position equivalent to PDB H241 in the nucleoside hydrolase of Crithidia fasciculate, 2MAS_A) as the general acid in the catalysis.
Comment:The majority of this group of IAG-nucleoside hydrolases possess a tryptophan residue , at a position equivalent to 1HP0_A, PDB 260; the inosine-uridine-preferring nucleoside hydrolase of Crithidia fasciculata has a catalytic histidine (H241)at this position.