title: Aspergillus niger protein EstA defines a new class of fungal esterases within the alpha/beta hydrolase fold superfamily of proteins.
abstract: From the fungus Aspergillus niger, we identified a new gene encoding protein EstA, a member of the alpha/beta-hydrolase fold superfamily but of unknown substrate specificity. EstA was overexpressed and its crystal structure was solved by molecular replacement using a lipase-acetylcholinesterase chimera template. The 2.1 A resolution structure of EstA reveals a canonical Ser/Glu/His catalytic triad located in a small pocket at the bottom of a large solvent-accessible, bowl-shaped cavity. Potential substrates selected by manual docking procedures were assayed for EstA activity. Consistent with the pocket geometry, preference for hydrolysis of short acyl/propyl chain substrates was found. Identification of close homologs from the genome of other fungi, of which some are broad host-range pathogens, defines EstA as the first member of a novel class of fungal esterases within the superfamily. Hence the structure of EstA constitutes a lead template in the design of new antifungal agents directed toward its pathogenic homologs.
authors.affiliation: Architecture et Fonction des Macromolécules Biologiques, CNRS UMR-6098, 31 Chemin Joseph Aiguier, F-13402 Marseille Cedex 20, France. yves@afmb.cnrs-mrs.fr
authors.forename: Yves
authors.initials: Y
authors.lastname: Bourne
authors.forename: Alinda A
authors.initials: AA
authors.lastname: Hasper
authors.forename: Henri
authors.initials: H
authors.lastname: Chahinian
authors.forename: Marianick
authors.initials: M
authors.lastname: Juin
authors.forename: Leo H
authors.initials: LH
authors.lastname: De Graaff
authors.forename: Pascale
authors.initials: P
authors.lastname: Marchot
mesh_terms: D001234:Aspergillus niger / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002265:Carboxylic Ester Hydrolases / Q000235:genetics / Q000378:metabolism*; D005810:Multigene Family; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D017422:Sequence Analysis, DNA; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D002265:Carboxylic Ester Hydrolases; C098953:EstA protein, bacteria