ArticleBiochemistry2014
Structural and kinetic characterization of guinea pig L-asparaginase type III.
Article in Biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Probing the Active Site of Class 3 L-Asparaginase by Mutagenesis: Mutations of the Ser-Lys Tandems of ReAV.Biomolecules · 2025Article
- 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
- Nonclinical Evaluation of Single-MutantInternational journal of molecular sciences · 2024Article
- Substrate Affinity Is Not Crucial for Therapeutic L-Asparaginases: Antileukemic Activity of Novel Bacterial Enzymes.Molecules (Basel, Switzerland) · 2024Article
- Deciphering Metabolic Pathways in High-Seeding-Density Fed-Batch Processes for Monoclonal Antibody Production: A Computational Modeling Perspective.Bioengineering (Basel, Switzerland) · 2024Article
- Biochemical characterization of L-asparaginase isoforms fromFrontiers in chemistry · 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
- Possible mechanism of metabolic and drug resistance with L-asparaginase therapy in childhood leukaemia.Frontiers in oncology · 2023Review
- Insights into the Distribution and Functional Properties of l-Asparaginase in the Archaeal Domain and Characterization ofACS omega · 2022Article
- 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
- Review
- Molecular Analysis of L-Asparaginases for Clarification of the Mechanism of Action and Optimization of Pharmacological Functions.Pharmaceutics · 2022Review
- Novel Insights on the Use of L-Asparaginase as an Efficient and Safe Anti-Cancer Therapy.Cancers · 2022Review
- Crystal structures of the elusive Rhizobium etli L-asparaginase reveal a peculiar active site.Nature communications · 2021Article
- Structural and biophysical aspects of l-asparaginases: a growing family with amazing diversity.IUCrJ · 2021Review
- Functional and structural evaluation of the antileukaemic enzyme L-asparaginase II expressed at low temperature by different Escherichia coli strains.Biotechnology letters · 2020Article
- Improving the Treatment of Acute Lymphoblastic Leukemia.Biochemistry · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
We investigated whether an uncharacterized protein from guinea pig could be the enzyme behind Kidd's serendipitous discovery, made over 60 years ago, that guinea pig serum has cell killing ability. It has been long known that an enzyme with l-asparaginase activity is responsible for cell killing, although astonishingly, its identity remains unclear. Bacterial asparaginases with similar cell killing properties have since become a mainstay therapy of certain cancers such as acute lymphoblastic leukemia. By hydrolyzing asparagine to aspartate and ammonia, these drugs deplete the asparagine present in the blood, killing cancer cells that rely on extracellular asparagine uptake for survival. However, bacterial asparaginases can elicit an adverse immune response. We propose that replacement of bacterial enzymes with the guinea pig asparaginase responsible for serum activity, by its virtue of being more closely related to human enzymes, will be less immunogenic. To this goal, we investigated whether an uncharacterized protein from guinea pig with putative asparaginase activity, which we call gpASNase3, could be that enzyme. We examined its self-activation process (gpASNase3 requires autocleavage to become active), kinetically characterized it for asparaginase and β-aspartyl dipeptidase activity, and elucidated its crystal structure in both the uncleaved and cleaved states. This work reveals that gpASNase3 is not the enzyme responsible for the antitumor effects of guinea pig serum. It exhibits a low affinity for asparagine as measured by a high Michaelis constant, KM, in the millimolar range, in contrast to the low KM (micromolar range) required for asparaginase to be effective as an anticancer agent.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.