Abstract:
:Trans-sialidases (TS) are GPI-anchored surface enzymes expressed in specific developmental stages of trypanosome parasites like Trypanosoma cruzi, the etiologic agent of Chagas disease, and T. brucei, the causative agent of sleeping sickness. TS catalyzes the transfer of sialic acid residues from host to parasite glycoconjugates through a transglycosidase reaction that appears to be critical for T. cruzi survival and cell invasion capability. We report here the structure of the T. cruzi trans-sialidase, alone and in complex with sugar ligands. Sialic acid binding is shown to trigger a conformational switch that modulates the affinity for the acceptor substrate and concomitantly creates the conditions for efficient transglycosylation. The structure provides a framework for the structure-based design of novel inhibitors with potential therapeutic applications.
journal_name
Mol Celljournal_title
Molecular cellauthors
Buschiazzo A,Amaya MF,Cremona ML,Frasch AC,Alzari PMdoi
10.1016/s1097-2765(02)00680-9subject
Has Abstractpub_date
2002-10-01 00:00:00pages
757-68issue
4eissn
1097-2765issn
1097-4164pii
S1097-2765(02)00680-9journal_volume
10pub_type
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