ArticleBiochemistry2023
2'-Deoxy Guanosine Nucleotides Alter the Biochemical Properties of Ras.
Article in Biochemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 7 citations in OpenAlex.
- Brønsted-basic small molecules activate GTP hydrolysis in KRAS-Q61 mutants.Nature chemical biology · 2026Article
- Real time characterization of the MAPK pathway using native mass spectrometry.Communications biology · 2025Article
- Adapting a Trapped Ion Mobility Spectrometry-Q-TOF for HighAnalytical chemistry · 2025Article
- Capturing RAS oligomerization on a membrane.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Molecular glue degrader for tumor treatment.Frontiers in oncology · 2024Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Ras proteins in the mitogen-activated protein kinase (MAPK) signaling pathway represent one of the most frequently mutated oncogenes in cancer. Ras binds guanosine nucleotides and cycles between active (GTP) and inactive (GDP) conformations to regulate the MAPK signaling pathway. Guanosine and other nucleotides exist in cells as either 2'-hydroxy or 2'-deoxy forms, and imbalances in the deoxyribonucleotide triphosphate pool have been associated with different diseases, such as diabetes, obesity, and cancer. However, the biochemical properties of Ras bound to dGNP are not well understood. Herein, we use native mass spectrometry to monitor the intrinsic GTPase activity of H-Ras and N-Ras oncogenic mutants, revealing that the rate of 2'-deoxy guanosine triphosphate (dGTP) hydrolysis differs compared to the hydroxylated form, in some cases by seven-fold. Moreover, K-Ras expressed from HEK293 cells exhibited a higher than anticipated abundance of dGNP, despite the low abundance of dGNP in cells. Additionally, the GTPase and dGTPase activity of K-Ras
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