Loiodice, Mélanie, Drula, Elodie, McIver, Zak et al. (16 more authors) (2025) Bacterial polysaccharide lyase family 33:Specificity from an evolutionarily conserved binding tunnel. Proceedings of the National Academy of Sciences of the United States of America. e2421623122. ISSN 1091-6490
Abstract
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | Polysaccharide-Lyases/metabolism,Substrate Specificity,Bacterial Proteins/metabolism,Bacteria/enzymology,Evolution, Molecular,Models, Molecular,Amino Acid Sequence,Binding Sites,Protein Binding,Polysaccharides/metabolism,Glycosaminoglycans/metabolism |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 19 Feb 2025 16:00 |
Last Modified: | 19 Feb 2025 17:10 |
Published Version: | https://doi.org/10.1073/pnas.2421623122 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1073/pnas.2421623122 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:223570 |
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Description: Bacterial polysaccharide lyase family 33: Specificity from an evolutionarily conserved binding tunnel
Licence: CC-BY 2.5