GTPase-activating proteins: Helping hands to complement an active site
Abstract
Stimulation of the intrinsic GTPase activity of GTP-binding proteins by GTPase-activating proteins (GAPs) is a basic principle of GTP-binding-protein downregulation. Recently, the molecular mechanism behind this reaction has been elucidated by studies on Ras and Rho, and their respective GAPs. The basic features involve stabilizing the existing catalytic machinery and supplementing it by an external arginine residue. This represents a novel mechanism for enzyme active-site formation.
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Most somatic mutations in KRAS impair GTPase function, leading to a persistent increase in RAS-GTP levels.
“most somatic mutations in KRAS impair this GTPase function, leading to a persistent increase in RAS-GTP levels.”
From The Role of KRAS Mutations in Colorectal Cancer: Biological Insights, Clinical Implications, and Future Therapeutic Perspectives (2025) · cites this paper as [11]
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- Authors
- Scheffzek, K., Ahmadian, M. R., & Wittinghofer, A.
- Affiliations
- Max Planck Society (DE)
- Venue
- Trends in Biochemical Sciences
- Publisher
- Elsevier BV
- Published
- 1998-07
- Volume
- 23
- Issue
- 7
- Pages
- 257-262
- ISSN
- 0968-0004 (ISSN-L)
- OpenAlex
- W1973728462
- Cited by
- 410
- References
- 57
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 2 · 2023: 6 · 2022: 6 · 2021: 10 · 2020: 5 · 2019: 3 · 2018: 7 · 2017: 7 · 2016: 9 · 2015: 6 · 2014: 11 · 2013: 9 · 2012: 20
- FWCI
- 2.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Biochemical Sciences (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- GTPase-activating protein, G proteins, GTPase activity, Ras, Rho, active site formation, arginine residues, enzyme catalysis, protein downregulation
- MeSH terms
- Amino Acid Sequence, Animals, Binding Sites, Enzyme Activation, Humans, Models, Biological, Models, Molecular, Protein Conformation, Proteins, Sequence Homology, Amino Acid, GTP Phosphohydrolases, GTPase-Activating Proteins, ras GTPase-Activating Proteins
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