ArticleBiochemistry2019
Intrinsic GTPase Activity of K-RAS Monitored by Native Mass Spectrometry.
Article in Biochemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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Who cites it
28 citing papers in PubMed, 38 citations in OpenAlex.
- Brønsted-basic small molecules activate GTP hydrolysis in KRAS-Q61 mutants.Nature chemical biology · 2026Article
- Time-Resolved Native Mass Spectrometry for Direct Measurement of Biomolecular Kinetics.Journal of the American Chemical Society · 2026Article
- SOS1: tracking the evolving path from promising to actionable therapeutic target in RAS-dependent cancers.Molecular cancer · 2026Review
- Prognostic Implications of Codon-SpecificJCO precision oncology · 2026Article
- Time-Resolved Crystallography Reveals the Mechanisms of GTP hydrolysis for N-RAS and the Oncogenic Mutants G12C, G12V and Q61L.bioRxiv : the preprint server for biology · 2025Article
- Real time characterization of the MAPK pathway using native mass spectrometry.Communications biology · 2025Article
- Deciphering allosteric mechanisms in KRAS activation: insights from GTP-induced conformational dynamics and interaction network reorganization.RSC advances · 2025Article
- Review
- Capturing RAS oligomerization on a membrane.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Native mass spectrometry and structural studies reveal modulation of MsbA-nucleotide interactions by lipids.Nature communications · 2024Article
- Farnesyl-transferase inhibitors show synergistic anticancer effects in combination with novel KRAS-G12C inhibitors.British journal of cancer · 2024Article
- Progress in Targeting KRAS Directly.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Advances in mass spectrometry to unravel the structure and function of protein condensates.Nature protocols · 2023Review
- Excited-state observation of active K-Ras reveals differential structural dynamics of wild-type versus oncogenic G12D and G12C mutants.Nature structural & molecular biology · 2023Article
- 2'-Deoxy Guanosine Nucleotides Alter the Biochemical Properties of Ras.Biochemistry · 2023Article
- Targeted therapies for KRAS-mutant non-small cell lung cancer: from preclinical studies to clinical development-a narrative review.Translational lung cancer research · 2023Review
- Variable-Temperature Native Mass Spectrometry for Studies of Protein Folding, Stabilities, Assembly, and Molecular Interactions.Annual review of biophysics · 2022Review
- High-Resolution Native Mass Spectrometry.Chemical reviews · 2022Review
- Approaches to Heterogeneity in Native Mass Spectrometry.Chemical reviews · 2022Review
- Intrinsically disordered proteins: Ensembles at the limits of Anfinsen's dogma.Biophysics reviews · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in RAS are associated with many different cancers and have been a therapeutic target for more than three decades. RAS cycles from an active to inactive state by both intrinsic and GTPase-activating protein (GAP)-stimulated hydrolysis. The activated enzyme interacts with downstream effectors, leading to tumor proliferation. Mutations in RAS associated with cancer are insensitive to GAP, and the rate of inactivation is limited to their intrinsic hydrolysis rate. Here, we use high-resolution native mass spectrometry (MS) to determine the kinetics and transition state thermodynamics of intrinsic hydrolysis for K-RAS and its oncogenic mutants. MS data reveal heterogeneity where both 2'-deoxy and 2'-hydroxy forms of GDP (guanosine diphosphate) and GTP (guanosine triphosphate) are bound to the recombinant enzyme. Intrinsic GTPase activity is directly monitored by the loss in mass of K-RAS bound to GTP, which corresponds to the release of phosphate. The rates determined from MS are in direct agreement with those measured using an established solution-based assay. Our results show that the transition state thermodynamics for the intrinsic GTPase activity of K-RAS is both enthalpically and entropically unfavorable. The oncogenic mutants G12C, Q61H, and G13D unexpectedly exhibit a 2'-deoxy GTP intrinsic hydrolysis rate higher than that for GTP.
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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.