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< | ==Inosine-Guanosine Nucleoside Hydrolase (IG-NH)== | ||
<StructureSection load='3fz0' size='340' side='right'caption='[[3fz0]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3fz0]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei Trypanosoma brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FZ0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FZ0 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]] 2.5Å</td></tr> | |||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</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=3fz0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fz0 OCA], [https://pdbe.org/3fz0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fz0 RCSB], [https://www.ebi.ac.uk/pdbsum/3fz0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fz0 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q57X73_TRYB2 Q57X73_TRYB2] | |||
== 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/fz/3fz0_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=3fz0 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Trypanosomes are purine-auxotrophic parasites that depend upon nucleoside hydrolase (NH) activity to salvage nitrogenous bases necessary for nucleic acid and cofactor synthesis. Nonspecific and purine-specific NHs have been widely studied, yet little is known about the 6-oxopurine-specific isozymes, although they are thought to play a primary role in the catabolism of exogenously derived nucleosides. Here, we report the first functional and structural characterization of the inosine-guanosine-specific NH from Trypanosoma brucei brucei. The enzyme shows near diffusion-limited efficiency coupled with a clear specificity for 6-oxopurine nucleosides achieved through a catalytic selection of these substrates. Pre-steady-state kinetic analysis reveals ordered product release, and a rate-limiting structural rearrangement that is associated with the release of the product, ribose. The crystal structure of this trypanosomal NH determined to 2.5 A resolution reveals distinctive features compared to those of both purine- and pyrimidine-specific isozymes in the framework of the conserved and versatile NH fold. Nanomolar iminoribitol-based inhibitors identified in this study represent important lead compounds for the development of novel therapeutic strategies against trypanosomal diseases. | |||
Structure and mechanism of the 6-oxopurine nucleosidase from Trypanosoma brucei brucei.,Vandemeulebroucke A, Minici C, Bruno I, Muzzolini L, Tornaghi P, Parkin DW, Versees W, Steyaert J, Degano M Biochemistry. 2010 Oct 19;49(41):8999-9010. PMID:20825170<ref>PMID:20825170</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3fz0" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Large Structures]] | ||
== | |||
< | |||
[[Category: | |||
[[Category: Trypanosoma brucei]] | [[Category: Trypanosoma brucei]] | ||
[[Category: Bruno | [[Category: Bruno I]] | ||
[[Category: Degano | [[Category: Degano M]] | ||
[[Category: Minici | [[Category: Minici C]] | ||
[[Category: Muzzolini | [[Category: Muzzolini L]] | ||
[[Category: Parkin | [[Category: Parkin DW]] | ||
[[Category: Schramm | [[Category: Schramm VL]] | ||
[[Category: Steyaert | [[Category: Steyaert J]] | ||
[[Category: Tornaghi | [[Category: Tornaghi P]] | ||
[[Category: Vandemeulebroucke | [[Category: Vandemeulebroucke A]] | ||
[[Category: Versees | [[Category: Versees W]] | ||
Latest revision as of 18:34, 1 November 2023
Inosine-Guanosine Nucleoside Hydrolase (IG-NH)Inosine-Guanosine Nucleoside Hydrolase (IG-NH)
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 PubMedTrypanosomes are purine-auxotrophic parasites that depend upon nucleoside hydrolase (NH) activity to salvage nitrogenous bases necessary for nucleic acid and cofactor synthesis. Nonspecific and purine-specific NHs have been widely studied, yet little is known about the 6-oxopurine-specific isozymes, although they are thought to play a primary role in the catabolism of exogenously derived nucleosides. Here, we report the first functional and structural characterization of the inosine-guanosine-specific NH from Trypanosoma brucei brucei. The enzyme shows near diffusion-limited efficiency coupled with a clear specificity for 6-oxopurine nucleosides achieved through a catalytic selection of these substrates. Pre-steady-state kinetic analysis reveals ordered product release, and a rate-limiting structural rearrangement that is associated with the release of the product, ribose. The crystal structure of this trypanosomal NH determined to 2.5 A resolution reveals distinctive features compared to those of both purine- and pyrimidine-specific isozymes in the framework of the conserved and versatile NH fold. Nanomolar iminoribitol-based inhibitors identified in this study represent important lead compounds for the development of novel therapeutic strategies against trypanosomal diseases. Structure and mechanism of the 6-oxopurine nucleosidase from Trypanosoma brucei brucei.,Vandemeulebroucke A, Minici C, Bruno I, Muzzolini L, Tornaghi P, Parkin DW, Versees W, Steyaert J, Degano M Biochemistry. 2010 Oct 19;49(41):8999-9010. PMID:20825170[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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