The sequence and crystal structure of the alpha-amino acid ester hydrolase from Xanthomonas citri define a new family of beta-lactam antibiotic acylases.
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.
Barends
Thomas R M
TR
Department of Biophysical Chemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, NL-9747 AG Groningen, The Netherlands.
Polderman-Tijmes
Jolanda J
JJ
Jekel
Peter A
PA
Hensgens
Charles M H
CM
de Vries
Erik J
EJ
Janssen
Dick B
DB
Dijkstra
Bauke W
BW
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
D002265:Carboxylic Ester Hydrolases; C058058:alpha-amino acid esterase