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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Acetylation
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Amidohydrolases / chemistry*
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Amidohydrolases / metabolism*
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Amino Acid Sequence
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Aspergillus fumigatus / enzymology*
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Aspergillus fumigatus / genetics
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Aspergillus fumigatus / physiology*
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Biofilms / growth & development*
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Catalytic Domain
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Conserved Sequence
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Fungal Proteins / chemistry*
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Fungal Proteins / metabolism*
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Gene Expression Regulation, Fungal
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Glycosaminoglycans / biosynthesis
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Metals / metabolism
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Polysaccharides / metabolism*
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Protein Domains
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Structural Homology, Protein
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Structure-Activity Relationship
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Substrate Specificity
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Time Factors
Substances
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Fungal Proteins
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Glycosaminoglycans
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Metals
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Polysaccharides
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Amidohydrolases