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| | ==Trypanosoma rangeli sialidase in complex with sialic acid== | | ==Trypanosoma rangeli sialidase in complex with sialic acid== |
| - | <StructureSection load='1n1y' size='340' side='right' caption='[[1n1y]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='1n1y' size='340' side='right'caption='[[1n1y]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1n1y]] 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=1N1Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1N1Y FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1n1y]] 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=1N1Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N1Y FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</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]] 2.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1mz6|1mz6]], [[1mz5|1mz5]], [[1n1s|1n1s]], [[1n1t|1n1t]], [[1n1v|1n1v]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</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=1n1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n1y OCA], [https://pdbe.org/1n1y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1n1y RCSB], [https://www.ebi.ac.uk/pdbsum/1n1y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1n1y 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=1n1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n1y OCA], [http://pdbe.org/1n1y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1n1y RCSB], [http://www.ebi.ac.uk/pdbsum/1n1y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1n1y 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]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n1/1n1y_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n1/1n1y_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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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: Nguyen, T]] | + | [[Category: Nguyen T]] |
| - | [[Category: Beta propeller]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Lectin-like fold]]
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| 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
The structure of the recombinant Trypanosoma rangeli sialidase (TrSA) has been determined at 1.6A resolution, and the structures of its complexes with the transition state analog inhibitor 2-deoxy-2,3-dehydro-N-acetyl-neuraminic acid (DANA), Neu-5-Ac-thio-alpha(2,3)-galactoside (NATG) and N-acetylneuraminic acid (NANA) have been determined at 1.64A, 2.1A and 2.85A, respectively. The 3D structure of TrSA is essentially identical to that of the natural enzyme, except for the absence of covalently attached sugar at five distinct N-glycosylation sites. The protein exhibits a topologically rigid active site architecture that is unaffected by ligand binding. The overall binding of DANA to the active site cleft is similar to that observed for other viral and bacterial sialidases, dominated by the interactions of the inhibitor carboxylate with the conserved arginine triad. However, the interactions of the other pyranoside ring substituents (hydroxyl, N-acetyl and glycerol moieties) differ between trypanosomal, bacterial and viral sialidases, providing a structural basis for specific inhibitor design. Sialic acid is found to bind the enzyme with the sugar ring in a distorted (half-chair or boat) conformation and the 2-OH hydroxyl group at hydrogen bonding distance of the carboxylate of Asp60, substantiating a direct catalytic role for this residue. A detailed comparison of TrSA with the closely related structure of T.cruzi trans-sialidase (TcTS) reveals a highly conserved catalytic center, where subtle structural differences account for strikingly different enzymatic activities and inhibition properties. The structure of TrSA in complex with NATG shows the active site cleft occupied by a smaller compound which could be identified as DANA, probably the product of a hydrolytic side reaction. Indeed, TrSA (but not TcTS) was found to cleave O and S-linked sialylated substrates, further stressing the functional differences between trypanosomal sialidases and trans-sialidases.
The high resolution structures of free and inhibitor-bound Trypanosoma rangeli sialidase and its comparison with T. cruzi trans-sialidase.,Amaya MF, Buschiazzo A, Nguyen T, Alzari PM J Mol Biol. 2003 Jan 24;325(4):773-84. PMID:12507479[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Amaya MF, Buschiazzo A, Nguyen T, Alzari PM. The high resolution structures of free and inhibitor-bound Trypanosoma rangeli sialidase and its comparison with T. cruzi trans-sialidase. J Mol Biol. 2003 Jan 24;325(4):773-84. PMID:12507479
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