9HYQ
BT984 a GH139 rhamnogalacturonan II exo-a-1,2-(2-Omethyl)-fucosidase
Summary for 9HYQ
| Entry DOI | 10.2210/pdb9hyq/pdb |
| Descriptor | DUF5703 domain-containing protein (2 entities in total) |
| Functional Keywords | glycoside hydrolases, gh139, microbiota, fucosidase, inverting, hydrolase |
| Biological source | Bacteroides thetaiotaomicron VPI-5482 |
| Total number of polymer chains | 2 |
| Total formula weight | 184860.34 |
| Authors | |
| Primary citation | McIver, Z.,Moraleda-Montoya, A.,Chen, Z.,Epa, R.,Starns, D.,Davy, M.,Garcia-Alija, M.,Basle, A.,Schubert, M.,Ndeh, D.,Trastoy, B.,Williams, S.J.,Guerin, M.E.,Cartmell, A. Understanding the substrate recognition and catalytic mechanism of methyl fucosidases from glycoside hydrolase family 139. J.Biol.Chem., :110407-110407, 2025 Cited by PubMed Abstract: Rhamnogalacturonan II is one of the most complex plant cell wall carbohydrates and is composed of 13 different sugars and 21 different glycosidic linkages. It is abundant in fruit and indulgence foods, such as chocolate and wine, making it common in the human diet. The human colonic commensal Bacteroides thetaiotaomicron expresses a consortium of 22 enzymes to metabolise rhamnogalacturonan II, some of which exclusively target sugars unique to rhamnogalacturonan II. Several of these enzyme families remain poorly described, and, consequently, our knowledge of rhamnogalacturonan II metabolism is limited. Chief among the poorly understood activities is glycoside hydrolase (GH) family 139, with targets α1,2-2O-methyl L-fucoside linkages, a sugar residue a sugar not found in any other plant cell wall complex glycans. Although the founding enzyme BT0984 was placed in the RG-II degradative pathway, no GH139 structure or catalytic blueprint had been available. We report the crystal structures of BT0984 and a second homologue, and reveal that the family operates with inverting stereochemistry. Using this data we undertook a mutagenic strategy, backed by molecular dynamics, to identify the important substrate binding and catalytic residues, mapping these residues throughout the GH139 family revealing the importance of the O2 methyl interaction of the substrate. We propose a catalytic mechanism that uses a non-canonical Asn as a catalytic base and shares similarity with L-fucosidases/L-galactosidases of family GH95. PubMed: 40544995DOI: 10.1016/j.jbc.2025.110407 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.7 Å) |
Structure validation
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