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2mas
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Nucleoside N-ribohydrolases are targets for disruption of purine salvage | + | 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 Structure== | ==About this Structure== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Degano, M.]] | [[Category: Degano, M.]] | ||
| - | [[Category: Sacchettini, J | + | [[Category: Sacchettini, J C.]] |
| - | [[Category: Schramm, V | + | [[Category: Schramm, V L.]] |
[[Category: CA]] | [[Category: CA]] | ||
[[Category: PIR]] | [[Category: PIR]] | ||
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[[Category: uridine]] | [[Category: uridine]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:07:26 2008'' |
Revision as of 16:07, 21 February 2008
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PURINE NUCLEOSIDE HYDROLASE WITH A TRANSITION STATE INHIBITOR
Overview
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 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.
Reference
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
Page seeded by OCA on Thu Feb 21 18:07:26 2008
