The 1.8 A structures of leech intramolecular trans-sialidase complexes: evidence of its enzymatic mechanism
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Updated: Oct 26, 2026

Production of Disulfide-stabilized Transmembrane Peptide Complexes for Structural Studies
Published on: March 6, 2013
1Center for Macromolecular Crystallography, University of Alabama at Birmingham, AL, 35294, USA.
Abstract:
Intramolecular trans-sialidase from leech (Macrobdella decora) is the first member of the sialidase superfamily found to exhibit strict specificity towards the cleavage of terminal Neu5Acalpha2-->3Gal linkage in sialoglycoconjugates. Its release of 2,7-anhydro-Neu5Ac instead of Neu5Ac indicates that it catalyzes an intramolecular trans-sialosyl reaction. Crystal structures of its complexes with an inactive substrate analogue 2-propenyl-Neu5Ac, and with the product 2,7-anhydro-Neu5Ac, have been determined to 1.8 A resolution. The boat conformation of the pyranose observed in the complexes supports the proposed enzymatic mechanism that O7 of an axial 6-glycerol group attacks the positively charged C2 of the intermediate. A generalized mechanism is proposed for the sialidase superfamily.
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