title: Reexamination of aspartoacylase: is this human enzyme really a glycoprotein?
abstract: Aspartoacylase catalyzes the metabolism of an important amino acid in the brain, with the release acetate serving as the source for fatty acid biosynthesis. Defects in this enzyme lead to a loss of activity and the symptoms of a fatal neurological disorder called Canavan disease. Extensive evidence, including deglycosylation studies, differential activity upon eukaryotic host expression and site directed mutagenesis, have supported the presence of a glycan that plays an essential role in the stability and catalytic activity of mammalian aspartoacylase. However, the structure of this enzyme did not show the presence of any non-amino acid components at the putative glycosylation site. A more extensive study specifically designed to resolve this discrepancy has now shown that recombinantly-expressed human aspartoacylase is not glycosylated, but is still fully functional and stable even when produced from a bacterial expression system. Alternative interpretations of the prior experiments now present a consistent picture of the structural components of this essential brain enzyme.
authors.affiliation: Department of Chemistry and Biochemistry, University of Toledo, Toledo, OH 43606, United States.
authors.forename: Qinzhe
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Chemistry and Biochemistry, University of Toledo, Toledo, OH 43606, United States. Electronic address: ron.viola@utoledo.edu.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Viola
mesh_terms: D000581:Amidohydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D017825:Canavan Disease / Q000201:enzymology; D003001:Cloning, Molecular; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009844:Oligosaccharides / Q000032:analysis; D010843:Pichia / Q000235:genetics; D017354:Point Mutation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D009844:Oligosaccharides; D011994:Recombinant Proteins; D000581:Amidohydrolases; C019751:aspartoacylase
keywords: Aspartoacylase; Deglycosylation; Glycoprotein