title: The 1.8 A structures of leech intramolecular trans-sialidase complexes: evidence of its enzymatic mechanism.
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.
authors.affiliation: Center for Macromolecular Crystallography, University of Alabama at Birmingham, AL, 35294, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Luo
authors.forename: S C
authors.initials: SC
authors.lastname: Li
authors.forename: Y T
authors.initials: YT
authors.lastname: Li
authors.forename: M
authors.initials: M
authors.lastname: Luo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid; D002384:Catalysis; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007865:Leeches / Q000201:enzymology; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D009439:Neuraminidase / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D014443:Tyrosine
chemical_list: D001224:Aspartic Acid; D014443:Tyrosine; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid