Loiodice, Mélanie, Drula, Elodie 
ORCID: 0000-0002-9168-5214, McIver, Zak ORCID: 0000-0002-4352-9049, Antonyuk, Svetlana ORCID: 0000-0002-2779-9946, Baslé, Arnaud ORCID: 0000-0002-4899-3086, Lima, Marcelo ORCID: 0000-0002-8952-3080, Yates, Edwin A ORCID: 0000-0001-9365-5433, Byrne, Dominic P, Coughlan, Jamie, Leech, Andrew ORCID: 0000-0001-6918-1469 et al (show 9 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, 122 (7).
e2421623122-.
ISSN 0027-8424, 1091-6490
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loiodice-et-al-2025-bacterial-polysaccharide-lyase-family-33-specificity-from-an-evolutionarily-conserved-binding-tunnel.pdf - Open Access published version Download (5MB) | Preview |
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.
| Item Type: | Article |
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| Uncontrolled Keywords: | Polysaccharide-Lyases, Glycosaminoglycans, Bacterial Proteins, Evolution, Molecular, Binding Sites, Amino Acid Sequence, Substrate Specificity, Models, Molecular |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 12 Feb 2025 16:00 |
| Last Modified: | 13 Aug 2025 10:12 |
| DOI: | 10.1073/pnas.2421623122 |
| Related Websites: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3190253 |
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