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

Natalie C. Bamford; François Le Mauff; Jaime C. Van Loon; Hanna Ostapska; Brendan D. Snarr; Yongzhen Zhang; Elena N. Kitova; John S. Klassen; Jeroen D. C. Codée; Donald C. Sheppard; P. Lynne Howell

doi:10.1038/s41467-020-16144-5

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

Natalie C. Bamford, François Le Mauff, Jaime C. Van Loon, Hanna Ostapska, Brendan D. Snarr, Yongzhen Zhang, Elena N. Kitova, John S. Klassen, Jeroen D. C. Codée, Donald C. Sheppard (Lead / Corresponding author), P. Lynne Howell (Lead / Corresponding author)

Molecular Microbiology

Research output: Contribution to journal › Article › peer-review

35 Citations (Scopus)

139 Downloads (Pure)

Abstract

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.

Original language	English
Article number	2450
Number of pages	13
Journal	Nature Communications
Volume	11
DOIs	https://doi.org/10.1038/s41467-020-16144-5
Publication status	Published - 15 May 2020

Keywords

Biofilms
Fungi
Glycobiology
X-ray crystallography

ASJC Scopus subject areas

General Physics and Astronomy
General Chemistry
General Biochemistry,Genetics and Molecular Biology

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10.1038/s41467-020-16144-5Licence: CC BY

Final Published VersionFinal published version, 2.48 MBLicence: CC BY

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Bamford, N. C., Le Mauff, F., Van Loon, J. C., Ostapska, H., Snarr, B. D., Zhang, Y., Kitova, E. N., Klassen, J. S., Codée, J. D. C., Sheppard, D. C., & Howell, P. L. (2020). Structural and biochemical characterization of the exopolysaccharide deacetylase Agd3 required for Aspergillus fumigatus biofilm formation. Nature Communications, 11, Article 2450. https://doi.org/10.1038/s41467-020-16144-5

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title = "Structural and biochemical characterization of the exopolysaccharide deacetylase Agd3 required for Aspergillus fumigatus biofilm formation",

abstract = "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.",

keywords = "Biofilms, Fungi, Glycobiology, X-ray crystallography",

author = "Bamford, {Natalie C.} and {Le Mauff}, Fran{\c c}ois and {Van Loon}, {Jaime C.} and Hanna Ostapska and Snarr, {Brendan D.} and Yongzhen Zhang and Kitova, {Elena N.} and Klassen, {John S.} and Cod{\'e}e, {Jeroen D. C.} and Sheppard, {Donald C.} and Howell, {P. Lynne}",

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doi = "10.1038/s41467-020-16144-5",

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AU - Bamford, Natalie C.

AU - Le Mauff, François

AU - Van Loon, Jaime C.

AU - Ostapska, Hanna

AU - Snarr, Brendan D.

AU - Zhang, Yongzhen

AU - Kitova, Elena N.

AU - Klassen, John S.

AU - Codée, Jeroen D. C.

AU - Sheppard, Donald C.

AU - Howell, P. Lynne

N1 - Natural Sciences and Engineering Research Council of Canada (Vanier, CGS-M) Cystic Fibrosis Canada (Studentship) Canadian Institutes of Health Research (123306, FDN-154327, 43998, 81361, FDN-159902) Fonds de Recherche du Québec - Santé (Distinguished Research Scholar) Canada Research Chairs Mary H. Beatty, and Dr. James A. and Connie P. Dickson Scholarships from the University of Toronto, The Hospital for Sick Children studentship

PY - 2020/5/15

Y1 - 2020/5/15

N2 - 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.

AB - 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.

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KW - X-ray crystallography

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M1 - 2450

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

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