ArticleACS chemical biology2010
Replacing Mn(2+) with Co(2+) in human arginase i enhances cytotoxicity toward l-arginine auxotrophic cancer cell lines.
Article in ACS chemical biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 50 papers.
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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.
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Who cites it
50 citing papers in PubMed, 117 citations in OpenAlex.
- Arginine deprivation induces prolonged autophagy activation and ROS-dependent cell death in glioblastoma multiforme.CNS oncology · 2026Article
- Arginine Deprivation of ASS1-Deficient Cancers Drives Mistranslation and Shared Neoepitope Production.Cancer research · 2026Article
- Arginine deprivation induces ROS dependent autophagic cell death in human acute myeloid leukemia cells.Human cell · 2026Article
- Peptide Arginases from Cryptic Pathways Install Ornithine Residues in Uncharacterized Members of Orphan RiPP Families.Chembiochem : a European journal of chemical biology · 2025Article
- The therapeutic potential of pegylated arginase I treatment in glioblastoma.Scientific reports · 2025Article
- Human 3D Lung Cancer Tissue Photothermal Therapy Using Zn- and Co-Doped Magnetite Nanoparticles.ACS biomaterials science & engineering · 2025Article
- Biochemistry, pharmacology, and in vivo function of arginases.Pharmacological reviews · 2025Review
- Broad-spectrum anti-cancer activity of fused human arginase variants.Investigational new drugs · 2024Article
- Efficacy and safety of pegzilarginase in arginase 1 deficiency (PEACE): a phase 3, randomized, double-blind, placebo-controlled, multi-centre trial.EClinicalMedicine · 2024Article
- Therapeutic potential of arginine deprivation therapy for gliomas: a systematic review of the existing literature.Frontiers in pharmacology · 2024Review
- Development and characterization of fused human arginase I for cancer therapy.Investigational new drugs · 2023Article
- Arginase inhibitory activities of guaiane sesquiterpenoids from Curcuma comosa rhizomes.Journal of natural medicines · 2023Article
- Human arginase I: a potential broad-spectrum anti-cancer agent.3 Biotech · 2023Review
- Structural and Biochemical Insights into Post-Translational Arginine-to-Ornithine Peptide Modifications by an Atypical Arginase.ACS chemical biology · 2023Article
- Human arginase 1, a Jack of all trades?3 Biotech · 2022Review
- Metabolic Reprogramming in Hematologic Malignancies: Advances and Clinical Perspectives.Cancer research · 2022Review
- Arginase: Mechanisms and Clinical Application in Hematologic Malignancy.Frontiers in oncology · 2022Review
- The past, present, and future of enzyme-based therapies.Drug discovery today · 2022Review
- Arginine depriving enzymes: applications as emerging therapeutics in cancer treatment.Cancer chemotherapy and pharmacology · 2021Review
- Metal-ion promiscuity of microbial enzyme DapE at its second metal-binding site.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Replacing the two Mn(2+) ions normally present in human Arginase I with Co(2+) resulted in a significantly lowered K(M) value without a concomitant reduction in k(cat). In addition, the pH dependence of the reaction was shifted from a pK(a) of 8.5 to a pK(a) of 7.5. The combination of these effects led to a 10-fold increase in overall catalytic activity (k(cat)/K(M)) at pH 7.4, close to the pH of human serum. Just as important for therapeutic applications, Co(2+) substitution lead to significantly increased serum stability of the enzyme. Our data can be explained by direct coordination of l-Arg to one of the Co(2+) ions during reaction, consistent with previously reported model studies. In vitro cytotoxicity experiments verified that the Co(2+)-substituted human Arg I displays an approximately 12- to 15-fold lower IC(50) value for the killing of human hepatocellular carcinoma and melanoma cell lines and thus constitutes a promising new candidate for the treatment of l-Arg auxotrophic tumors.
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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.