1MZ6

Trypanosoma rangeli sialidase in complex with the inhibitor DANA

Summary for 1MZ6

• Entry DOI: 10.2210/pdb1mz6/pdb
• Related: 1MR5 1MS0 1MS1 1MS3 1MS4 1MS5 1MS8 1MS9 1MZ5
• Descriptor: sialidase, 2-acetamido-2-deoxy-beta-D-glucopyranose, 2-DEOXY-2,3-DEHYDRO-N-ACETYL-NEURAMINIC ACID, ... (4 entities in total)
• Functional Keywords: inibitor complex, trypanosomal sialidase, sialyltransferase, hydrolase, hydrolase inhibitor
• Biological source: Trypanosoma rangeli
• Total number of polymer chains: 1
• Total formula weight: 71102.74

Authors

Buschiazzo, A.,Tavares, G.A.,Campetella, O.,Spinelli, S.,Cremona, M.L.,Paris, G.,Amaya, M.F.,Frasch, A.C.C.,Alzari, P.M. (deposition date: 2002-10-05, release date: 2002-10-16, Last modification date: 2024-11-13)

Primary citation

Buschiazzo, A.,Tavares, G.A.,Campetella, O.,Spinelli, S.,Cremona, M.L.,Paris, G.,Amaya, M.F.,Frasch, A.C.C.,Alzari, P.M.
Structural basis of sialyltransferase activity in trypanosomal sialidases
Embo J., 19:16-24, 2000

PubMed Abstract: The intracellular parasite Trypanosoma cruzi, the etiological agent of Chagas disease, sheds a developmentally regulated surface trans-sialidase, which is involved in key aspects of parasite-host cell interactions. Although it shares a common active site architecture with bacterial neuraminidases, the T.cruzi enzyme behaves as a highly efficient sialyltransferase. Here we report the crystal structure of the closely related Trypanosoma rangeli sialidase and its complex with inhibitor. The enzyme folds into two distinct domains: a catalytic beta-propeller fold tightly associated with a lectin-like domain. Comparison with the modeled structure of T.cruzi trans-sialidase and mutagenesis experiments allowed the identification of amino acid substitutions within the active site cleft that modulate sialyltransferase activity and suggest the presence of a distinct binding site for the acceptor carbohydrate. The structures of the Trypanosoma enzymes illustrate how a glycosidase scaffold can achieve efficient glycosyltransferase activity and provide a framework for structure-based drug design.

PubMed: 10619840
DOI: 10.1093/emboj/19.1.16

Experimental method

X-RAY DIFFRACTION (2.9 Å)