ArticleBiochemistry2006
Characterization of human aspartoacylase: the brain enzyme responsible for Canavan disease.
Article in Biochemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 50 citations in OpenAlex.
- The Emerging Role of N-Acetylaspartate in Cancer.International journal of molecular sciences · 2026Review
- A genome-wide association study identifies Asian-specific genetic susceptibility for epigenetic age acceleration.GeroScience · 2026Article
- Neuroglial Pathophysiology of Leukodystrophies.Advances in neurobiology · 2025Review
- Perspectives of aminoacylases in biocatalytic synthesis of N-acyl-amino acids surfactants.Applied microbiology and biotechnology · 2024Review
- Deep mutational scanning reveals a correlation between degradation and toxicity of thousands of aspartoacylase variants.Nature communications · 2024Article
- Cellular and molecular mechanisms of aspartoacylase and its role in Canavan disease.Cell & bioscience · 2024Review
- Clinically Distinct Phenotypes of Canavan Disease Correlate with Residual Aspartoacylase Enzyme Activity.Human mutation · 2017Article
- Enhanced brain distribution of modified aspartoacylase.Molecular genetics and metabolism · 2014Article
- N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) promote growth and inhibit differentiation of glioma stem-like cells.The Journal of biological chemistry · 2013Article
- Relationship between enzyme properties and disease progression in Canavan disease.Journal of inherited metabolic disease · 2013Article
- A structural and functional analysis of Nna1 in Purkinje cell degeneration (pcd) mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2012Article
- Modification of aspartoacylase for potential use in enzyme replacement therapy for the treatment of Canavan disease.Molecular genetics and metabolism · 2011Article
- Structures of aminoacylase 3 in complex with acetylated substrates.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Mouse aminoacylase 3: a metalloenzyme activated by cobalt and nickel.Biochimica et biophysica acta · 2009Article
- Examination of the mechanism of human brain aspartoacylase through the binding of an intermediate analogue.Biochemistry · 2008Article
- Structures of proteins of biomedical interest from the Center for Eukaryotic Structural Genomics.Journal of structural and functional genomics · 2007Review
- N-Acetyl-D-glucosamine-6-phosphate deacetylase: substrate activation via a single divalent metal ion.Biochemistry · 2007Article
- Mutational analysis of aspartoacylase: implications for Canavan disease.Brain research · 2007Article
- Structure of aspartoacylase, the brain enzyme impaired in Canavan disease.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- The impact of structural biology on neurobiology.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Aspartoacylase catalyzes the deacetylation of N-acetylaspartic acid (NAA) to produce acetate and L-aspartate and is the only brain enzyme that has been shown to effectively metabolize NAA. Although the exact role of this enzymatic reaction has not yet been completely elucidated, the metabolism of NAA appears to be necessary in the formation of myelin lipids, and defects in this enzyme lead to Canavan disease, a fatal neurological disorder. The low catalytic activity and inherent instability observed with the Escherichia coli-expressed form of aspartoacylase suggested the need for a suitable eukaryotic expression system that would be capable of producing a fully functional, mature enzyme. Human aspartoacylase has now been successfully expressed in Pichia pastoris. While the expression yields are lower than in E. coli, the purified enzyme is significantly more stable. This enzyme form has the same substrate specificity but is 150-fold more active than the E. coli-expressed enzyme. The molecular weight of the purified enzyme, measured by mass spectrometry, is higher than predicted, suggesting the presence of some post-translational modifications. Deglycosylation of aspartoacylase or mutation at the glycosylation site causes decreased enzyme stability and diminished catalytic activity. A carbohydrate component has been removed and characterized by mass spectrometry. In addition to this carbohydrate moiety, the enzyme has also been shown to contain one zinc atom per subunit. Chelation studies to remove the zinc result in a reversible loss of catalytic activity, thus establishing aspartoacylase as a zinc metalloenzyme.
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