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8R72

Polysaccharide lyase BtPL33HA (BT4410) Y291A with HA dp4 collected at 1.33 A

Summary for 8R72
Entry DOI10.2210/pdb8r72/pdb
DescriptorHeparinase, beta-D-glucopyranuronic acid-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-beta-D-glucopyranuronic acid-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose, ZINC ION, ... (4 entities in total)
Functional Keywordspolysaccharide lyase, glycosaminoglycan, hyaluronic acid, conformational change, lyase
Biological sourceBacteroides thetaiotaomicron VPI-5482
Total number of polymer chains2
Total formula weight148821.02
Authors
Cartmell, A. (deposition date: 2023-11-23, release date: 2024-12-04, Last modification date: 2025-03-05)
Primary citationLoiodice, M.,Drula, E.,McIver, Z.,Antonyuk, S.,Basle, A.,Lima, M.,Yates, E.A.,Byrne, D.P.,Coughlan, J.,Leech, A.,Mesdaghi, S.,Rigden, D.J.,Drouillard, S.,Helbert, W.,Henrissat, B.,Terrapon, N.,Wright, G.S.A.,Couturier, M.,Cartmell, A.
Bacterial polysaccharide lyase family 33: Specificity from an evolutionarily conserved binding tunnel.
Proc.Natl.Acad.Sci.USA, 122:e2421623122-e2421623122, 2025
Cited by
PubMed 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.
PubMed: 39932998
DOI: 10.1073/pnas.2421623122
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.58 Å)
Structure validation

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