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Lookup NU author(s): Dr Arnaud Basle
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Copyright © 2025 the Author(s).Acidic glycans are essential for the biology of multicellular eukaryotes. To utilize them, microbial life including symbionts and pathogens has evolved polysaccharide lyases (PL) that cleave their 1,4 glycosidic linkages via a β-elimination mechanism. PL family 33 (PL33) enzymes have the unusual ability to target a diverse range of glycosaminoglycans (GAGs), as well as the bacterial polymer, gellan gum. In order to gain more detailed insight into PL33 activities we recombinantly expressed 10 PL33 members derived from all major environments and further elucidated the detailed biochemical and biophysical properties of five, showing that their substrate specificity is conferred by variations in tunnel length and topography. The key amino acids involved in catalysis and substrate interactions were identified, and employing a combination of complementary biochemical, structural, and modeling approaches, we show that the tunnel topography is induced by substrate binding to the glycan. Structural and bioinformatic analyses revealed that these features are conserved across several lyase families as well as in mammalian GAG epimerases.
Author(s): Loiodice M, Drula E, McIver Z, Antonyuk S, Basle A, Lima M, Yates EA, Byrne DP, Coughlan J, Leech A, Mesdaghi S, Rigden DJ, Drouillard S, Helbert W, Henrissat B, Terrapon N, Wright GSA, Couturier M, Cartmell A
Publication type: Article
Publication status: Published
Journal: Proceedings of the National Academy of Sciences of the United States of America
Year: 2025
Volume: 122
Issue: 7
Print publication date: 18/02/2025
Online publication date: 11/02/2025
Acceptance date: 29/12/2024
Date deposited: 04/03/2025
ISSN (print): 0027-8424
ISSN (electronic): 1091-6490
Publisher: National Academy of Sciences
URL: https://doi.org/10.1073/pnas.2421623122
DOI: 10.1073/pnas.2421623122
Data Access Statement: The crystal structure dataset generated has been deposited in the Protein Data Bank (PDB) under the following accession numbers: 8R75 (47), 8R6Z (48), 8R70 (49), 8R71 (50), 8R72 (51), and 8R73 (52). Information on all other data and materials is contained within the main manuscript and supplemental information.
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