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2mas

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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'''
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===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.
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{{ABSTRACT_PUBMED_9572842}}
==About this Structure==
==About this Structure==
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[[Category: Purine nucleoside hydrolase]]
[[Category: Purine nucleoside hydrolase]]
[[Category: Uridine]]
[[Category: Uridine]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 09:31:46 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 15:27:24 2008''

Revision as of 12:27, 28 July 2008

Image:2mas.png

Template:STRUCTURE 2mas

PURINE NUCLEOSIDE HYDROLASE WITH A TRANSITION STATE INHIBITOR

Template:ABSTRACT PUBMED 9572842

About this Structure

2MAS is a Single protein structure of sequence from Crithidia fasciculata. 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

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