1wcs | pdb_00001wcs

A MUTANT OF TRYPANOSOMA RANGELI SIALIDASE DISPLAYING TRANS-SIALIDASE ACTIVITY

spinqualitylabelsall models 1wcs, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1wcs is a 1 chain structure with sequence from Tryra. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 1mz5, 1mz6, 1n1s, 1n1t, 1n1v, 1n1y Activity: Exo-alpha-sialidase, with EC number 3.2.1.18 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum 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 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.

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