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| | ==Trypanosoma rangeli Sialidase in Complex with 2-Keto-3-deoxy-D-glycero-D-galacto-2,3-difluoro-nononic acid (2,3-difluoro-KDN)== | | ==Trypanosoma rangeli Sialidase in Complex with 2-Keto-3-deoxy-D-glycero-D-galacto-2,3-difluoro-nononic acid (2,3-difluoro-KDN)== |
| - | <StructureSection load='2ags' size='340' side='right' caption='[[2ags]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='2ags' size='340' side='right'caption='[[2ags]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ags]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Tryra Tryra]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AGS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AGS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ags]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_rangeli Trypanosoma rangeli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AGS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AGS FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FKD:3-DEOXY-3-FLUORO-D-ERYTHRO-ALPHA-L-MANNO-NON-2-ULOPYRANOSONIC+ACID'>FKD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.7Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1n1s|1n1s]], [[2a75|2a75]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FKD:3-DEOXY-3-FLUORO-D-ERYTHRO-ALPHA-L-MANNO-NON-2-ULOPYRANOSONIC+ACID'>FKD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Exo-alpha-sialidase Exo-alpha-sialidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.18 3.2.1.18] </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=2ags FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ags OCA], [https://pdbe.org/2ags PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ags RCSB], [https://www.ebi.ac.uk/pdbsum/2ags PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ags ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ags FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ags OCA], [http://pdbe.org/2ags PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ags RCSB], [http://www.ebi.ac.uk/pdbsum/2ags PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ags ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/O44049_TRYRA O44049_TRYRA] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Exo-alpha-sialidase]] | + | [[Category: Large Structures]] |
| - | [[Category: Tryra]] | + | [[Category: Trypanosoma rangeli]] |
| - | [[Category: Alzari, P M]] | + | [[Category: Alzari PM]] |
| - | [[Category: Amaya, M F]] | + | [[Category: Amaya MF]] |
| - | [[Category: Buschiazzo, A]] | + | [[Category: Buschiazzo A]] |
| - | [[Category: Beta-propeller]]
| + | |
| - | [[Category: Beta-sandwich]]
| + | |
| - | [[Category: Covalent enzyme-intermediate complex]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
O44049_TRYRA
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
Trypanosoma rangeli sialidase is a glycoside hydrolase (family GH33) that catalyzes the cleavage of alpha-2-->3-linked sialic acid residues from sialoglycoconjugates with overall retention of anomeric configuration. Retaining glycosidases usually operate through a ping-pong mechanism, wherein a covalent intermediate is formed between the carbohydrate and an active site carboxylic acid of the enzyme. Sialidases, instead, appear to use a tyrosine as the catalytic nucleophile, leaving the possibility of an essentially different catalytic mechanism. Indeed, a direct nucleophilic role for a tyrosine was shown for the homologous trans-sialidase from Trypanosoma cruzi, although itself not a typical sialidase. Here we present the three-dimensional structures of the covalent glycosyl-enzyme complexes formed by the T. rangeli sialidase with two different mechanism-based inactivators at 1.9 and 1.7 Angstroms resolution. To our knowledge, these are the first reported structures of enzymatically competent covalent intermediates for a strictly hydrolytic sialidase. Kinetic analyses have been carried out on the formation and turnover of both intermediates, showing that structural modifications to these inactivators can be used to modify the lifetimes of covalent intermediates. These results provide further evidence that all sialidases likely operate through a similar mechanism involving the transient formation of a covalently sialylated enzyme. Furthermore, we believe that the ability to "tune" the inactivation and reactivation rates of mechanism-based inactivators toward specific enzymes represents an important step toward developing this class of inactivators into therapeutically useful compounds.
Structural and kinetic analysis of two covalent sialosyl-enzyme intermediates on Trypanosoma rangeli sialidase.,Watts AG, Oppezzo P, Withers SG, Alzari PM, Buschiazzo A J Biol Chem. 2006 Feb 17;281(7):4149-55. Epub 2005 Nov 18. PMID:16298994[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Watts AG, Oppezzo P, Withers SG, Alzari PM, Buschiazzo A. Structural and kinetic analysis of two covalent sialosyl-enzyme intermediates on Trypanosoma rangeli sialidase. J Biol Chem. 2006 Feb 17;281(7):4149-55. Epub 2005 Nov 18. PMID:16298994 doi:http://dx.doi.org/10.1074/jbc.M510677200
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