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== | ==Inosine-Adenosine-Guanosine Preferring Nucleoside Hydrolase From Trypanosoma vivax: Trp260Ala Mutant In Complex With 3-Deaza-Adenosine== | ||
[[1r4f]] is a 2 chain structure with sequence from [ | <StructureSection load='1r4f' size='340' side='right'caption='[[1r4f]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1r4f]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_vivax Trypanosoma vivax]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R4F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1R4F 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=AD3:3-DEAZA-ADENOSINE'>AD3</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=1r4f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r4f OCA], [https://pdbe.org/1r4f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1r4f RCSB], [https://www.ebi.ac.uk/pdbsum/1r4f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1r4f ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q9GPQ4_TRYVI Q9GPQ4_TRYVI] | |||
== 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/r4/1r4f_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=1r4f ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
General acid catalysis is a powerful and widely used strategy in enzymatic nucleophilic displacement reactions. For example, hydrolysis/phosphorolysis of the N-glycosidic bond in nucleosides and nucleotides commonly involves the protonation of the leaving nucleobase concomitant with nucleophilic attack. However, in the nucleoside hydrolase of the parasite Trypanosoma vivax, crystallographic and mutagenesis studies failed to identify a general acid. This enzyme binds the purine base of the substrate between the aromatic side-chains of Trp83 and Trp260. Here, we show via quantum chemical calculations that face-to-face stacking can raise the pKa of a heterocyclic aromatic compound by several units. Site-directed mutagenesis combined with substrate engineering demonstrates that Trp260 catalyzes the cleavage of the glycosidic bond by promoting the protonation of the purine base at N-7, hence functioning as an alternative to general acid catalysis. | |||
Leaving group activation by aromatic stacking: an alternative to general acid catalysis.,Versees W, Loverix S, Vandemeulebroucke A, Geerlings P, Steyaert J J Mol Biol. 2004 Apr 16;338(1):1-6. PMID:15050818<ref>PMID:15050818</ref> | |||
<ref | |||
[[Category: | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
<div class="pdbe-citations 1r4f" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Trypanosoma vivax]] | [[Category: Trypanosoma vivax]] | ||
[[Category: Geerlings | [[Category: Geerlings P]] | ||
[[Category: Loverix | [[Category: Loverix S]] | ||
[[Category: Steyaert | [[Category: Steyaert J]] | ||
[[Category: Vandemeulebroucke | [[Category: Vandemeulebroucke A]] | ||
[[Category: Versees | [[Category: Versees W]] | ||
Latest revision as of 09:00, 23 August 2023
Inosine-Adenosine-Guanosine Preferring Nucleoside Hydrolase From Trypanosoma vivax: Trp260Ala Mutant In Complex With 3-Deaza-AdenosineInosine-Adenosine-Guanosine Preferring Nucleoside Hydrolase From Trypanosoma vivax: Trp260Ala Mutant In Complex With 3-Deaza-Adenosine
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedGeneral acid catalysis is a powerful and widely used strategy in enzymatic nucleophilic displacement reactions. For example, hydrolysis/phosphorolysis of the N-glycosidic bond in nucleosides and nucleotides commonly involves the protonation of the leaving nucleobase concomitant with nucleophilic attack. However, in the nucleoside hydrolase of the parasite Trypanosoma vivax, crystallographic and mutagenesis studies failed to identify a general acid. This enzyme binds the purine base of the substrate between the aromatic side-chains of Trp83 and Trp260. Here, we show via quantum chemical calculations that face-to-face stacking can raise the pKa of a heterocyclic aromatic compound by several units. Site-directed mutagenesis combined with substrate engineering demonstrates that Trp260 catalyzes the cleavage of the glycosidic bond by promoting the protonation of the purine base at N-7, hence functioning as an alternative to general acid catalysis. Leaving group activation by aromatic stacking: an alternative to general acid catalysis.,Versees W, Loverix S, Vandemeulebroucke A, Geerlings P, Steyaert J J Mol Biol. 2004 Apr 16;338(1):1-6. PMID:15050818[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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