Arabidopsis thaliana RAC/ROP GTPases constitute a plant specific Rho GTPase family in the RAS superfamily, which has been implicated in numerous pivotal signalling cascades in plants. Research has shown that plants in some cases have evolved different modes of regulating Rho GTPase activity as compared to the equivalent systems in animals and yeast. In order to gain structural insight into plant signaling at the molecular level, we have determined the first crystal structure of a RAC-like GTPase belonging to the RAS superfamily from the plant kingdom. The structure of AtRAC7/ROP9 bound to GDP was solved at a resolution of 1.78 A. We have found that the structure of plant Rho GTPases is based upon a conserved G-domain architecture, but structural differences were found concerning the insert region and switch II region of the protein.
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http://dx.doi.org/10.1016/j.phytochem.2006.08.011 | DOI Listing |
Bioorg Chem
January 2025
Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700026, India. Electronic address:
Histone deacetylases (HDACs) play a critical role in chromatin remodelling and modulating the activity of various histone proteins. Aberrant HDAC functions has been related to the progression of breast cancer (BC), making HDAC inhibitors (HDACi) promising small-molecule therapeutics for its treatment. Hydroxamic acid (HA) is a significant pharmacophore due to its strong metal-chelating ability, HDAC inhibition properties, MMP inhibition abilities, and more.
View Article and Find Full Text PDFNat Commun
January 2025
Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, QC, H3T 1J4, Canada.
Intense research on founding members of the RAS superfamily has defined our understanding of these critical signalling proteins, leading to the premise that small GTPases function as molecular switches dependent on differential nucleotide loading. The closest homologs of H/K/NRAS are the three-member RRAS family, and interest in the MRAS GTPase as a regulator of MAPK activity has recently intensified. We show here that MRAS does not function as a classical switch and is unable to exchange GDP-to-GTP in solution or when tethered to a lipid bilayer.
View Article and Find Full Text PDFJ Mol Biol
February 2025
Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; University of Cincinnati College of Medicine, Cincinnati, OH, USA. Electronic address:
Rho family GTPases are a part of the Ras superfamily and are signaling hubs for many cellular processes. While the detailed understanding of Ras structure and function has led to tremendous progress in oncogenic Ras-targeted drug discovery, studies of the related Rho GTPases are still catching up as the recurrent cancer-related Rho GTPase mutations have only been discovered in the last decade. Like that of Ras, an in-depth understanding of the structural basis of how Rho GTPases and their mutants behave as key oncogenic drivers benefits the development of clinically effective therapies.
View Article and Find Full Text PDFCommun Chem
November 2024
Department of Chemistry and Biochemistry, College of Arts and Sciences, University of South Carolina, Columbia, SC, USA.
Maintaining body homeostasis is the ultimate key to health. There are rich resources of bioactive materials for the functionality of homeostatic modulators (HMs) from both natural and synthetic chemical repertories. HMs are powerful modern therapeutics for human diseases including neuropsychiatric diseases, mental disorders, and drug addiction (e.
View Article and Find Full Text PDFSci Rep
November 2024
Institut pour la Recherche sur le Cancer de Lille, Place de Verdun, 59054, Lille, France.
The RhoH protein is a member of the Ras superfamily of guanosine triphosphate-binding proteins. RhoH is an atypical Rho family member that is always GTP-bound and thus always activated. It is restrictively expressed in normal hematopoietic cells, where it is a negative regulator of cell growth and survival.
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