Reexamination of aspartoacylase: Is this human enzyme really a glycoprotein?

Wang, Qinzhe; Viola, Ronald E.

doi:10.1016/j.abb.2014.03.001

Cited by 3 publications

(2 citation statements)

References 17 publications

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“…We analyzed the effects of 12 novel ASPA missense mutations (detected in a total of 14 patients) as well as two common missense mutations (p.Glu285Ala and p.Ala305Glu). The 14 variants were transiently transfected into HEK293 cells, which are considered the most suitable system to study ASPA variants because it ensures the availability of all necessary codons [Wang and Viola, ].…”

Section: Discussionmentioning

confidence: 99%

“…Residues Arg168 and Tyr288 stabilize the binding of NAA to ASPA. It was shown that due to rare codon usage, eukaryotic expression systems need to be used to properly study enzyme variants [Wang and Viola, 2014]. The vast majority of ASPA mutations that have been overexpressed in COS or human embryonic kidney (HEK)293 cells present very low enzyme activity (lower than 5% of wild-type (WT)) [Janson et al, 2006;Sommer and Sass, 2012;Surendran et al, 2003a].…”

Section: Introductionmentioning

confidence: 99%

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Clinically Distinct Phenotypes of Canavan Disease Correlate with Residual Aspartoacylase Enzyme Activity

et al. 2017

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We describe 14 patients with 12 novel missense mutations in ASPA, the gene causing Canavan disease (CD). We developed a method to study the effect of these 12 variants on the function of aspartoacylase—the hydrolysis of N‐acetyl‐l‐aspartic acid (NAA) to aspartate and acetate. The wild‐type ASPA open reading frame (ORF) and the ORFs containing each of the variants were transfected into HEK293 cells. Enzyme activity was determined by incubating cell lysates with NAA and measuring the released aspartic acid by LC–MS/MS. Clinical data were obtained for 11 patients by means of questionnaires. Four patients presented with a non‐typical clinical picture or with the milder form of CD, whereas seven presented with severe CD. The mutations found in the mild patients corresponded to the variants with the highest residual enzyme activities, suggesting that this assay can help evaluate unknown variants found in patients with atypical presentation. We have detected a correlation between clinical presentation, enzyme activity, and genotype for CD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinically Distinct Phenotypes of Canavan Disease Correlate with Residual Aspartoacylase Enzyme Activity

et al. 2017

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Purification and characterization of aspartate N-acetyltransferase: A critical enzyme in brain metabolism

Wang

Zhao

Parungao

et al. 2016

Protein Expression and Purification

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Aspartoacylase: a central nervous system enzyme. Structure, catalytic activity and regulation mechanisms

Kots¹,

Khrenova²,

Nemukhin³

et al. 2019

Russ. Chem. Rev.

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Aspartoacylase is a key enzyme in the human central nervous system. Catalytic deficiency of aspartoacylase is associated with several neurodegenerative disorders, which accounts for the enhanced interest in description of the catalytic action and regulatory mechanisms of this enzyme. This review focuses on molecular modelling of the catalytic function of aspartoacylase and the ways of its allosteric regulation in terms of modern theoretical chemistry approaches. The conclusions based on experimental data on the structure and functions of aspartoacylase accumulated during the last 20 years and conclusions drawn from computer modelling results of the last 5 years are analyzed in detail. The bibliography includes 109 references.

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Reexamination of aspartoacylase: Is this human enzyme really a glycoprotein?

Cited by 3 publications

References 17 publications

Clinically Distinct Phenotypes of Canavan Disease Correlate with Residual Aspartoacylase Enzyme Activity

Clinically Distinct Phenotypes of Canavan Disease Correlate with Residual Aspartoacylase Enzyme Activity

Purification and characterization of aspartate N-acetyltransferase: A critical enzyme in brain metabolism

Aspartoacylase: a central nervous system enzyme. Structure, catalytic activity and regulation mechanisms

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