1MS9

Triclinic form of Trypanosoma cruzi trans-sialidase, in complex with lactose

Summary for 1MS9

• Entry DOI: 10.2210/pdb1ms9/pdb
• Related: 1MR5 1MS0 1MS1 1MS3 1MS4 1MS5 1MS8 1MZ5 1MZ6
• Related PRD ID: PRD_900004
• Descriptor: trans-sialidase, beta-D-galactopyranose-(1-4)-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: sialidase, trans-glycosylation, protein-acrbohydrate interactions, beta-propeller, hydrolase
• Biological source: Trypanosoma cruzi
• Total number of polymer chains: 2
• Total formula weight: 143463.11

Authors

Buschiazzo, A.,Amaya, M.F.,Cremona, M.L.,Frasch, A.C.,Alzari, P.M. (deposition date: 2002-09-19, release date: 2003-03-25, Last modification date: 2021-10-27)

Primary citation

Buschiazzo, A.,Amaya, M.F.,Cremona, M.L.,Frasch, A.C.,Alzari, P.M.
The crystal structure and mode of action of trans-sialidase, a key enzyme of Trypanosoma cruzi pathogenesis
Mol.Cell, 10:757-768, 2002

PubMed 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.

PubMed: 12419220
DOI: 10.1016/S1097-2765(02)00680-9

Experimental method

X-RAY DIFFRACTION (1.58 Å)