View source for 1wcs


==A mutant of Trypanosoma rangeli sialidase displaying trans-sialidase activity==
<StructureSection load='1wcs' size='340' side='right'caption='[[1wcs]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1wcs]] 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=1WCS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WCS 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]] 2.8&#8491;</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=1wcs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wcs OCA], [https://pdbe.org/1wcs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wcs RCSB], [https://www.ebi.ac.uk/pdbsum/1wcs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wcs ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/O44049_TRYRA O44049_TRYRA] 
== 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/wc/1wcs_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1wcs ConSurf].
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== Publication Abstract from PubMed ==
Trypanosoma cruzi, the agent of Chagas disease, expresses a modified sialidase, the trans-sialidase, which transfers sialic acid from host glycoconjugates to beta-galactose present in parasite mucins. Another American trypanosome, Trypanosoma rangeli, expresses a homologous protein that has sialidase activity but is devoid of transglycosidase activity. Based on the recently determined structures of T.rangeli sialidase (TrSA) and T.cruzi trans-sialidase (TcTS), we have now constructed mutants of TrSA with the aim of studying the relevant residues in transfer activity. Five mutations, Met96-Val, Ala98-Pro, Ser120-Tyr, Gly249-Tyr and Gln284-Pro, were enough to obtain a sialidase mutant (TrSA(5mut)) with trans-sialidase activity; and a sixth mutation increased the activity to about 10% that of wild-type TcTS. The crystal structure of TrSA(5mut) revealed the formation of a trans-sialidase-like binding site for the acceptor galactose, primarily defined by the phenol group of Tyr120 and the indole ring of Trp313, which adopts a new conformation, similar to that in TcTS, induced by the Gln284-Pro mutation. The transition state analogue 2,3-didehydro-2-deoxy-N-acetylneuraminic acid (DANA), which inhibits sialidases but is a poor inhibitor of trans-sialidase, was used to probe the active site conformation of mutant enzymes. The results show that the presence of a sugar acceptor binding-site, the fine-tuning of protein-substrate interactions and the flexibility of crucial active site residues are all important to achieve transglycosidase activity from the TrSA sialidase scaffold.

A sialidase mutant displaying trans-sialidase activity.,Paris G, Ratier L, Amaya MF, Nguyen T, Alzari PM, Frasch AC J Mol Biol. 2005 Jan 28;345(4):923-34. PMID:15588836<ref>PMID:15588836</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Trypanosoma rangeli]]
[[Category: Alzari PM]]
[[Category: Amaya MF]]
[[Category: Frasch C]]
[[Category: Nguyen T]]
[[Category: Paris G]]
[[Category: Ratier L]]