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== | ==PURINE NUCLEOSIDE HYDROLASE WITH A TRANSITION STATE INHIBITOR== | ||
<StructureSection load='2mas' size='340' side='right'caption='[[2mas]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2mas]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Crithidia_fasciculata Crithidia fasciculata]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MAS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MAS FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PIR:2-(4-AMINO-PHENYL)-5-HYDROXYMETHYL-PYRROLIDINE-3,4-DIOL'>PIR</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2mas FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mas OCA], [https://pdbe.org/2mas PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mas RCSB], [https://www.ebi.ac.uk/pdbsum/2mas PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mas ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/IUNH_CRIFA IUNH_CRIFA] Catalyzes the hydrolysis of all of the commonly occurring purine and pyrimidine nucleosides into ribose and the associated base, but has a preference for inosine and uridine as substrates. | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ma/2mas_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2mas ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | 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. | ||
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<ref>PMID:9572842</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2mas" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Crithidia fasciculata]] | [[Category: Crithidia fasciculata]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Degano M]] | |||
[[Category: Degano | [[Category: Sacchettini JC]] | ||
[[Category: Sacchettini | [[Category: Schramm VL]] | ||
[[Category: Schramm | |||
Latest revision as of 09:45, 9 August 2023
PURINE NUCLEOSIDE HYDROLASE WITH A TRANSITION STATE INHIBITORPURINE NUCLEOSIDE HYDROLASE WITH A TRANSITION STATE INHIBITOR
Structural highlights
FunctionIUNH_CRIFA Catalyzes the hydrolysis of all of the commonly occurring purine and pyrimidine nucleosides into ribose and the associated base, but has a preference for inosine and uridine as substrates. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedNucleoside 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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