2mas
PURINE NUCLEOSIDE HYDROLASE WITH A TRANSITION STATE INHIBITOR
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| , resolution 2.3Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | , , and | ||||||
| Ligands: | and | ||||||
| Gene: | IU-NH FROM C. FASCICULATA (Crithidia fasciculata) | ||||||
| Activity: | Purine nucleosidase, with EC number 3.2.2.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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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