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Inverting family GH156 sialidases define an unusual catalytic motif for glycosidase action

DOI: 10.1038/s41467-019-12684-7 DOI Help

Authors: Pedro Bule (University of York) , Léa Chuzel (New England Biolabs) , Elena Blagova (University of York) , Liang Wu (University of York) , Melissa A. Gray (Stanford University) , Bernard Henrissat (Architecture et Fonction des Macromolécules Biologiques (AFMB), Centre National de la Recherche Scientifique (CNRS, UMR7257), Institut National Agronomique (INRA, USC 1408) and Aix-Marseille Université (AMU)) , Erdmann Rapp (Max Planck Institute for Dynamics of Complex Technical Systems; glyXera GmbH) , Carolyn R. Bertozzi (Stanford University) , Christopher H. Taron (New England Biolabs) , Gideon J. Davies (University of York)
Co-authored by industrial partner: Yes

Type: Journal Paper
Journal: Nature Communications , VOL 10

State: Published (Approved)
Published: October 2019
Diamond Proposal Number(s): 18598

Open Access Open Access

Abstract: Sialic acids are a family of related sugars that play essential roles in many biological events intimately linked to cellular recognition in both health and disease. Sialidases are therefore orchestrators of cellular biology and important therapeutic targets for viral infection. Here, we sought to define if uncharacterized sialidases would provide distinct paradigms in sialic acid biochemistry. We show that a recently discovered sialidase family, whose first member EnvSia156 was isolated from hot spring metagenomes, defines an unusual structural fold and active centre constellation, not previously described in sialidases. Consistent with an inverting mechanism, EnvSia156 reveals a His/Asp active center in which the His acts as a Brønsted acid and Asp as a Brønsted base in a single-displacement mechanism. A predominantly hydrophobic aglycone site facilitates accommodation of a variety of 2-linked sialosides; a versatility that offers the potential for glycan hydrolysis across a range of biological and technological platforms.

Journal Keywords: Carbohydrates; Chemical biology; Enzyme mechanisms; Glycobiology; X-ray crystallography

Subject Areas: Chemistry, Biology and Bio-materials


Instruments: I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography

Documents:
s41467-019-12684-7.pdf