Works (3)
Updated: April 23rd, 2025 19:03
2023 article
Allosteric site variants affect GTP hydrolysis on Ras
Johnson, C. W., Fetics, S. K., Davis, K. P., Rodrigues, J. A., & Mattos, C. (2023, August 24). Protein Science.
author keywords: allosteric site; allostery; HRAS; hydrolysis; KRAS; mutation; RAF; small GTPase
MeSH headings : Humans; Allosteric Site; Hydrolysis; raf Kinases / chemistry; raf Kinases / genetics; raf Kinases / metabolism; ras Proteins / genetics; ras Proteins / metabolism; Guanosine Triphosphate / metabolism
topics (OpenAlex): Protein Kinase Regulation and GTPase Signaling; Enzyme Structure and Function; Cellular transport and secretion
TL;DR:
It is shown that closure of the allosteric site correlates with increased hydrolysis of GTP on HRAS in solution, and this behavior may be representative of a cluster of poorly understood mutations that occur in human tumors, which potentially cooperate with RAF complex formation to stabilize the GTP-bound state of RAS.
(via Semantic Scholar)
open access via onlinelibrary.wiley.com (publisher PDF)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
8. Decent Work and Economic Growth
(OpenAlex)
Source: Web Of Science
Added: January 2, 2024
2015 article
Allosteric Effects of the Oncogenic RasQ61L Mutant on Raf-RBD
Fetics, S. K., Guterres, H., Kearney, B. M., Buhrman, G., Ma, B., Nussinov, R., & Mattos, C. (2015, February 12). Structure.
MeSH headings : Allosteric Regulation; Catalytic Domain; Crystallography, X-Ray; Humans; Hydrogen Bonding; Molecular Dynamics Simulation; Mutation, Missense; Protein Binding; Protein Interaction Domains and Motifs; Protein Structure, Quaternary; Protein Structure, Secondary; Proto-Oncogene Proteins c-raf / chemistry; Proto-Oncogene Proteins p21(ras) / chemistry; Proto-Oncogene Proteins p21(ras) / genetics
topics (OpenAlex): Nuclear Receptors and Signaling; Heat shock proteins research; Coenzyme Q10 studies and effects
TL;DR:
In addition to local perturbations on Ras, RasQ61L has substantial long-range effects on the Ras allosteric lobe and on Raf-RBD, which is essential for the activation of the Raf kinase domain through a currently unknown mechanism.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Source: Web Of Science
Added: August 6, 2018
2010 article
Allosteric modulation of Ras positions Q61 for a direct role in catalysis
Buhrman, G., Holzapfel, G., Fetics, S., & Mattos, C. (2010, March 1). Proceedings of the National Academy of Sciences.
author keywords: GTPase; Raf; calcium; intrinsic hydrolysis
MeSH headings : Acetates / pharmacology; Allosteric Regulation / drug effects; Allosteric Site; Biocatalysis / drug effects; Calcium / metabolism; Calcium Compounds / pharmacology; Catalytic Domain; Crystallography, X-Ray; Enzyme Stability / drug effects; Glutamine / metabolism; Hydrogen Bonding / drug effects; Hydrolysis / drug effects; Hydroxyl Radical / metabolism; Magnesium / metabolism; Models, Molecular; Protein Structure, Tertiary; Structure-Activity Relationship; ras Proteins / chemistry; ras Proteins / metabolism
topics (OpenAlex): Protein Kinase Regulation and GTPase Signaling; Melanoma and MAPK Pathways; Enzyme Structure and Function
TL;DR:
This structure suggests a direct catalytic role for Q61 where it interacts with a water molecule that bridges one of the γ-phosphate oxygen atoms to the hydroxyl group of Y32 to stabilize the transition state of the hydrolysis reaction.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
6. Clean Water and Sanitation
(OpenAlex)
Source: Web Of Science
Added: August 6, 2018