title: The sequence and crystal structure of the alpha-amino acid ester hydrolase from Xanthomonas citri define a new family of beta-lactam antibiotic acylases.
abstract: alpha-Amino acid ester hydrolases (AEHs) catalyze the hydrolysis and synthesis of esters and amides with an alpha-amino group. As such, they can synthesize beta-lactam antibiotics from acyl compounds and beta-lactam nuclei obtained from the hydrolysis of natural antibiotics. This article describes the gene sequence and the 1.9-A resolution crystal structure of the AEH from Xanthomonas citri. The enzyme consists of an alpha/beta-hydrolase fold domain, a helical cap domain, and a jellyroll beta-domain. Structural homology was observed to the Rhodococcus cocaine esterase, indicating that both enzymes belong to the same class of bacterial hydrolases. Docking of a beta-lactam antibiotic in the active site explains the substrate specificity, specifically the necessity of an alpha-amino group on the substrate, and explains the low specificity toward the beta-lactam nucleus.
authors.affiliation: Department of Biophysical Chemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, NL-9747 AG Groningen, The Netherlands.
authors.forename: Thomas R M
authors.initials: TR
authors.lastname: Barends
authors.forename: Jolanda J
authors.initials: JJ
authors.lastname: Polderman-Tijmes
authors.forename: Peter A
authors.initials: PA
authors.lastname: Jekel
authors.forename: Charles M H
authors.initials: CM
authors.lastname: Hensgens
authors.forename: Erik J
authors.initials: EJ
authors.lastname: de Vries
authors.forename: Dick B
authors.initials: DB
authors.lastname: Janssen
authors.forename: Bauke W
authors.initials: BW
authors.lastname: Dijkstra
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry* / Q000235:genetics; D018360:Crystallography, X-Ray; D015698:Genomic Library; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D016959:Xanthomonas campestris / Q000201:enzymology* / Q000235:genetics
chemical_list: D002265:Carboxylic Ester Hydrolases; C058058:alpha-amino acid esterase