2mas: Difference between revisions
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==Overview== | ==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 .. | 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== | ||
2MAS is a | 2MAS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Crithidia_fasciculata Crithidia fasciculata] with CA and PIR as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Purine_nucleosidase Purine nucleosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.1 3.2.2.1] Structure known Active Sites: S1, S2, S3 and S4. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2MAS OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: uridine]] | [[Category: uridine]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 13:46:32 2007'' | ||
