Structural highlights
Function
[IUNH_CRIFA] Catalyzes the hydrolysis of all of the commonly occurring purine and pyrimidine nucleosides into ribose and the associated base, but has a preference for inosine and uridine as substrates.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Nucleoside N-ribohydrolases are targets for disruption of purine salvage in the protozoan parasites. The structure of a trypanosomal N-ribohydrolase in complex with a transition-state inhibitor is reported at 2.3 A resolution. The nonspecific nucleoside hydrolase from Crithidia fasciculata cocrystallized with p-aminophenyliminoribitol reveals tightly bound Ca2+ as a catalytic site ligand. The complex with the transition-state inhibitor is characterized by (1) large protein conformational changes to create a hydrophobic leaving group site (2) C3'-exo geometry for the inhibitor, typical of a ribooxocarbenium ion (3) stabilization of the ribooxocarbenium analogue between the neighboring group 5'-hydroxyl and bidentate hydrogen bonds to Asn168; and (4) octacoordinate Ca2+ orients a catalytic site water and is liganded to two hydroxyls of the inhibitor. The mechanism is ribooxocarbenium stabilization with weak leaving group activation and is a departure from glucohydrolases which use paired carboxylates to achieve the transition state.
Trypanosomal nucleoside hydrolase. A novel mechanism from the structure with a transition-state inhibitor.,Degano M, Almo SC, Sacchettini JC, Schramm VL Biochemistry. 1998 May 5;37(18):6277-85. PMID:9572842[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Degano M, Almo SC, Sacchettini JC, Schramm VL. Trypanosomal nucleoside hydrolase. A novel mechanism from the structure with a transition-state inhibitor. Biochemistry. 1998 May 5;37(18):6277-85. PMID:9572842 doi:http://dx.doi.org/10.1021/bi973012e
