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1wcs

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1wcs, resolution 2.80Å ()
Activity: Exo-alpha-sialidase, with EC number 3.2.1.18
Related: 1mz5, 1mz6, 1n1s, 1n1t, 1n1v, 1n1y
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



A MUTANT OF TRYPANOSOMA RANGELI SIALIDASE DISPLAYING TRANS-SIALIDASE ACTIVITY

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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

1wcs is a 1 chain structure with sequence from Trypanosoma rangeli. Full crystallographic information is available from OCA.

Reference

  • Paris G, Ratier L, Amaya MF, Nguyen T, Alzari PM, Frasch AC. A sialidase mutant displaying trans-sialidase activity. J Mol Biol. 2005 Jan 28;345(4):923-34. PMID:15588836 doi:10.1016/j.jmb.2004.09.031

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