2mas
PURINE NUCLEOSIDE HYDROLASE WITH A TRANSITION STATE INHIBITOR
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OverviewOverview
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.
About this StructureAbout this Structure
2MAS is a Single protein structure of sequence from Crithidia fasciculata with and as ligands. Active as Purine nucleosidase, with EC number 3.2.2.1 Known structural/functional Sites: , , and . Full crystallographic information is available from OCA.
ReferenceReference
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
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