The Biochemical Impact of Extracting an Embedded Adenylate Kinase Domain Using Circular Permutation
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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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Correction to: Naturehttps://doi.org/10.1038/s41586-024-08455-0 Published online 22 January 2025. In the version of the article initially published, the affiliations of Hana A. Chang (Department of Plant and Microbial Biology, University of California Berkeley, Berkeley, CA, USA) and Ron Milo (Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot, Israel) were incorrect and have now been amended in the HTML and PDF versions of the article.