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| {{STRUCTURE_2mas| PDB=2mas | SCENE= }} | | {{STRUCTURE_2mas| PDB=2mas | SCENE= }} |
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| '''PURINE NUCLEOSIDE HYDROLASE WITH A TRANSITION STATE INHIBITOR'''
| | ===PURINE NUCLEOSIDE HYDROLASE WITH A TRANSITION STATE INHIBITOR=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_9572842}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 9572842 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_9572842}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Purine nucleoside hydrolase]] | | [[Category: Purine nucleoside hydrolase]] |
| [[Category: Uridine]] | | [[Category: Uridine]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 09:31:46 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 15:27:24 2008'' |