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| | <StructureSection load='3fz0' size='340' side='right'caption='[[3fz0]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='3fz0' size='340' side='right'caption='[[3fz0]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3fz0]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_(trypanozoon)_brucei Trypanosoma (trypanozoon) 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> | + | <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='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> | + | </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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2mas|2mas]], [[1kic|1kic]], [[1q8f|1q8f]], [[3b9x|3b9x]]</div></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tb927.7.4570 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5691 Trypanosoma (Trypanozoon) brucei])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Purine_nucleosidase Purine nucleosidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.1 3.2.2.1] </span></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> | | <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> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q57X73_TRYB2 Q57X73_TRYB2] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Purine nucleosidase]] | + | [[Category: Trypanosoma brucei]] |
| - | [[Category: Bruno, I]] | + | [[Category: Bruno I]] |
| - | [[Category: Degano, M]] | + | [[Category: Degano M]] |
| - | [[Category: Minici, C]] | + | [[Category: Minici C]] |
| - | [[Category: Muzzolini, L]] | + | [[Category: Muzzolini L]] |
| - | [[Category: Parkin, D W]] | + | [[Category: Parkin DW]] |
| - | [[Category: Schramm, V L]] | + | [[Category: Schramm VL]] |
| - | [[Category: Steyaert, J]] | + | [[Category: Steyaert J]] |
| - | [[Category: Tornaghi, P]] | + | [[Category: Tornaghi P]] |
| - | [[Category: Vandemeulebroucke, A]] | + | [[Category: Vandemeulebroucke A]] |
| - | [[Category: Versees, W]] | + | [[Category: Versees W]] |
| - | [[Category: Glycosidase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Nh fold]]
| + | |
| - | [[Category: Open alpha/beta structure]]
| + | |
| Structural highlights
Function
Q57X73_TRYB2
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 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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Vandemeulebroucke A, Minici C, Bruno I, Muzzolini L, Tornaghi P, Parkin DW, Versees W, Steyaert J, Degano M. Structure and mechanism of the 6-oxopurine nucleosidase from Trypanosoma brucei brucei. Biochemistry. 2010 Oct 19;49(41):8999-9010. PMID:20825170 doi:10.1021/bi100697d
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