ArticleChemistry & biology2013
Free glycine accelerates the autoproteolytic activation of human asparaginase.
Article in Chemistry & biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Unveiling the Catalytic Mechanism and Conformational Dynamics of Guinea Pig l‑Asparaginase Type 1 for Leukemia Drug Design.ACS catalysis · 2025Article
- Towards a dependable data set of structures for L-asparaginase research.Acta crystallographica. Section D, Structural biology · 2024Article
- Elucidation of the Active Form and Reaction Mechanism in Human Asparaginase Type III Using Multiscale Simulations.Journal of chemical information and modeling · 2023Article
- The effects of nature-inspired amino acid substitutions on structural and biochemical properties of the E. coli L-asparaginase EcAIII.Protein science : a publication of the Protein Society · 2023Article
- Thermo-L-Asparaginases: From the Role in the Viability of Thermophiles and Hyperthermophiles at High Temperatures to a Molecular Understanding of Their Thermoactivity and Thermostability.International journal of molecular sciences · 2023Review
- Structural and biophysical studies of new L-asparaginase variants: lessons from random mutagenesis of the prototypic Escherichia coli Ntn-amidohydrolase.Acta crystallographica. Section D, Structural biology · 2022Article
- Temperature dependent autocleavage and applications of recombinant L-asparaginase from3 Biotech · 2022Article
- Highly Active Thermophilic L-Asparaginase fromInternational journal of molecular sciences · 2021Article
- Structural and biophysical aspects of l-asparaginases: a growing family with amazing diversity.IUCrJ · 2021Review
- Bacillus sonorensis L. Asparaginase: Cloning, Expression in E. coli and Characterization.The protein journal · 2020Article
- Improving the Treatment of Acute Lymphoblastic Leukemia.Biochemistry · 2020Article
- Characterization of Three L-Asparaginases from Maritime Pine (Frontiers in plant science · 2017Article
- Identification of Small Molecule Compounds for Pharmacological Chaperone Therapy of Aspartylglucosaminuria.Scientific reports · 2016Article
- Intramolecular Cleavage of the hASRGL1 Homodimer Occurs in Two Stages.Biochemistry · 2016Article
- Exploring the role of conformational heterogeneity in cis-autoproteolytic activation of ThnT.Biochemistry · 2014Article
- Elucidation of the specific function of the conserved threonine triad responsible for human L-asparaginase autocleavage and substrate hydrolysis.Journal of molecular biology · 2014Article
- Human 60-kDa lysophospholipase contains an N-terminal L-asparaginase domain that is allosterically regulated by L-asparagine.The Journal of biological chemistry · 2014Article
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6 authors at 2 institutions in 2 countries.
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Abstract
Human asparaginase 3 (hASNase3), which belongs to the N-terminal nucleophile hydrolase superfamily, is synthesized as a single polypeptide that is devoid of asparaginase activity. Intramolecular autoproteolytic processing releases the amino group of Thr168, a moiety required for catalyzing asparagine hydrolysis. Recombinant hASNase3 purifies as the uncleaved, asparaginase-inactive form and undergoes self-cleavage to the active form at a very slow rate. Here, we show that the free amino acid glycine selectively acts to accelerate hASNase3 cleavage both in vitro and in human cells. Other small amino acids such as alanine, serine, or the substrate asparagine are not capable of promoting autoproteolysis. Crystal structures of hASNase3 in complex with glycine in the uncleaved and cleaved enzyme states reveal the mechanism of glycine-accelerated posttranslational processing and explain why no other amino acid can substitute for glycine.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.