Structural and biochemical characterization of the exopolysaccharide deacetylase Agd3 required for Aspergillus fumigatus biofilm formation.

Autor: Bamford NC; Program in Molecular Medicine, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.; Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada.; Division of Molecular Microbiology, School of Life Sciences, University of Dundee, DD1 5EH, Dundee, UK., Le Mauff F; Department of Microbiology and Immunology, Faculty of Medicine, McGill University, Montreal, QC, H3A 2B4, Canada.; Infectious Disease and Immunity in Global Health, Research Institute of McGill University Health Center, Montreal, QC, H4A 3J1, Canada.; McGill Interdisciplinary Initiative in Infection and Immunity, Montreal, QC, H3A 1Y2, Canada., Van Loon JC; Program in Molecular Medicine, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.; Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada., Ostapska H; Department of Microbiology and Immunology, Faculty of Medicine, McGill University, Montreal, QC, H3A 2B4, Canada.; Infectious Disease and Immunity in Global Health, Research Institute of McGill University Health Center, Montreal, QC, H4A 3J1, Canada.; McGill Interdisciplinary Initiative in Infection and Immunity, Montreal, QC, H3A 1Y2, Canada., Snarr BD; Department of Microbiology and Immunology, Faculty of Medicine, McGill University, Montreal, QC, H3A 2B4, Canada.; Infectious Disease and Immunity in Global Health, Research Institute of McGill University Health Center, Montreal, QC, H4A 3J1, Canada.; McGill Interdisciplinary Initiative in Infection and Immunity, Montreal, QC, H3A 1Y2, Canada., Zhang Y; Leiden Institute of Chemistry, Leiden University, 2300RA, Leiden, The Netherlands., Kitova EN; Alberta Glycomics Centre and Department of Chemistry, University of Alberta, Edmonton, AB, T6G 2G2, Canada., Klassen JS; Alberta Glycomics Centre and Department of Chemistry, University of Alberta, Edmonton, AB, T6G 2G2, Canada., Codée JDC; Leiden Institute of Chemistry, Leiden University, 2300RA, Leiden, The Netherlands., Sheppard DC; Department of Microbiology and Immunology, Faculty of Medicine, McGill University, Montreal, QC, H3A 2B4, Canada. donald.sheppard@mcgill.ca.; Infectious Disease and Immunity in Global Health, Research Institute of McGill University Health Center, Montreal, QC, H4A 3J1, Canada. donald.sheppard@mcgill.ca.; McGill Interdisciplinary Initiative in Infection and Immunity, Montreal, QC, H3A 1Y2, Canada. donald.sheppard@mcgill.ca., Howell PL; Program in Molecular Medicine, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada. howell@sickkids.ca.; Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada. howell@sickkids.ca.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2020 May 15; Vol. 11 (1), pp. 2450. Date of Electronic Publication: 2020 May 15.
DOI: 10.1038/s41467-020-16144-5
Abstrakt: The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Deletion of a gene encoding a putative deacetylase, Agd3, leads to defects in GAG deacetylation, biofilm formation, and virulence. Here, we show that Agd3 deacetylates GAG in a metal-dependent manner, and is the founding member of carbohydrate esterase family CE18. The active site is formed by four catalytic motifs that are essential for activity. The structure of Agd3 includes an elongated substrate-binding cleft formed by a carbohydrate binding module (CBM) that is the founding member of CBM family 87. Agd3 homologues are encoded in previously unidentified putative bacterial exopolysaccharide biosynthetic operons and in other fungal genomes.
Databáze: MEDLINE