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.
Nat Commun. 2020 May 15;11(1):2450. doi: 10.1038/s41467-020-16144-5.
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.
真菌病原体烟曲霉的重要毒力因子是胞外多糖半乳氨基半乳糖（GAG）。缺失一个编码假定去乙酰化酶的基因 Agd3 会导致 GAG 去乙酰化、生物膜形成和毒力缺陷。在这里，我们表明 Agd3 以金属依赖的方式去乙酰化 GAG，并且是碳水化合物酯酶家族 CE18 的创始成员。活性位点由四个对活性至关重要的催化基序组成。Agd3 的结构包括一个由碳水化合物结合模块（CBM）形成的拉长的底物结合裂缝，CBM 是 CBM 家族 87 的创始成员。Agd3 同源物编码在以前未被识别的假定细菌胞外多糖生物合成操纵子和其他真菌基因组中。
