ArticleProceedings of the National Academy of Sciences of the United States of America1992
X-ray crystal structures of transforming p21 ras mutants suggest a transition-state stabilization mechanism for GTP hydrolysis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1992. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 129 citations in OpenAlex.
- Mechanistic insights on spatiotemporal control of Ras-signaling.Biological chemistry · 2026Review
- Structures and Functions of the Human GATOR1 Complex.Sub-cellular biochemistry · 2024Review
- Mediating kinase activity in Ras-mutant cancer: potential for an individualised approach?Frontiers in pharmacology · 2024Review
- Emerging role of small GTPases and their interactome in plants to combat abiotic and biotic stress.Protoplasma · 2023Review
- Review
- Review
- The RAS-interacting chaperone UNC119 drives the RASSF6-MDM2-p53 axis and antagonizes RAS-mediated malignant transformation.The Journal of biological chemistry · 2020Article
- Structural Insights into the Regulation Mechanism of Small GTPases by GEFs.Molecules (Basel, Switzerland) · 2019Review
- A germline mutation in Rab43 gene identified from a cancer family predisposes to a hereditary liver-colon cancer syndrome.BMC cancer · 2019Article
- Water Distribution within Wild-Type NRas Protein and Q61 Mutants during Unrestrained QM/MM Dynamics.Biophysical journal · 2018Article
- The reactivity-driven biochemical mechanism of covalent KRASNature structural & molecular biology · 2018Article
- Molecular control of Rab activity by GEFs, GAPs and GDI.Small GTPases · 2018Review
- The Rho GTPase signalling pathway in urothelial carcinoma.Nature reviews. Urology · 2018Review
- Protein Regulation in Signal Transduction.Cold Spring Harbor perspectives in biology · 2016Review
- Adenylylation of Tyr77 stabilizes Rab1b GTPase in an active state: A molecular dynamics simulation analysis.Scientific reports · 2016Article
- Interaction of a novel fluorescent GTP analogue with the small G-protein K-Ras.Journal of biochemistry · 2016Article
- Structures of Drosophila melanogaster Rab2 and Rab3 bound to GMPPNP.Acta crystallographica. Section F, Structural biology communications · 2015Article
- Allosteric modulation of Ras and the PI3K/AKT/mTOR pathway: emerging therapeutic opportunities.Frontiers in physiology · 2014Review
- Lessons from computer simulations of Ras proteins in solution and in membrane.Biochimica et biophysica acta · 2013Review
- The Role of Gln61 in HRas GTP hydrolysis: a quantum mechanics/molecular mechanics study.Biophysical journal · 2012Article
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Authors and funding
7 authors at 1 institution in 1 country.
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Abstract
RAS genes isolated from human tumors often have mutations at positions corresponding to amino acid 12 or 61 of the encoded protein (p21), while retroviral ras-encoded p21 contains substitutions at both positions 12 and 59. These mutant proteins are deficient in their GTP hydrolysis activity, and this loss of activity is linked to their transforming potential. The crystal structures of the mutant proteins are presented here as either GDP-bound or GTP-analogue-bound complexes. Based on these structures, a mechanism for the p21 GTPase reaction is proposed that is consistent with the observed structural and biochemical data. The central feature of this mechanism is a specific stabilization complex formed between the Gln-61 side-chain and the pentavalent gamma-phosphate of the GTP transition state. Amino acids other than glutamine at position 61 cannot stabilize the transition state, and amino acids larger than glycine at position 12 would interfere with the transition-state complex. Thr-59 disrupts the normal position of residue 61, thus preventing its participation in the transition-state complex.
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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.