Ras conformational ensembles, allostery, and signaling

S Lu, H Jang, S Muratcioglu, A Gursoy, O Keskin… - Chemical …, 2016 - ACS Publications
Ras proteins are classical members of small GTPases that function as molecular switches by
alternating between inactive GDP-bound and active GTP-bound states. Ras activation is …

The K-Ras, N-Ras, and H-Ras isoforms: unique conformational preferences and implications for targeting oncogenic mutants

JA Parker, C Mattos - Cold Spring Harbor …, 2018 - perspectivesinmedicine.cshlp.org
Ras controls a multitude of cellular signaling processes, including cell proliferation,
differentiation, and apoptosis. Deregulation of Ras cycling often promotes tumorigenesis …

Motorless transport of microtubules along tubulin, RanGTP, and salt gradients

S Shim, B Gouveia, B Ramm, VA Valdez… - Nature …, 2024 - nature.com
Microtubules are dynamic filaments that assemble spindles for eukaryotic cell division. As
the concentration profiles of soluble tubulin and regulatory proteins are non-uniform during …

Structures of N-terminally processed KRAS provide insight into the role of N-acetylation

S Dharmaiah, TH Tran, S Messing, C Agamasu… - Scientific reports, 2019 - nature.com
Although post-translational modification of the C-terminus of RAS has been studied
extensively, little is known about N-terminal processing. Mass spectrometric characterization …

K-Ras populates conformational states differently from its isoform H-Ras and oncogenic mutant K-RasG12D

JA Parker, AY Volmar, S Pavlopoulos, C Mattos - Structure, 2018 - cell.com
Structures of wild-type K-Ras from crystals obtained in the presence of guanosine
triphosphate (GTP) or its analogs have remained elusive. Of the K-Ras mutants, only K …

Isothermal chemical denaturation assay for monitoring protein stability and inhibitor interactions

R Mahran, N Vello, A Komulainen, M Malakoutikhah… - Scientific Reports, 2023 - nature.com
Thermal shift assay (TSA) with altered temperature has been the most widely used method
for monitoring protein stability for drug research. However, there is a pressing need for …

GTP hydrolysis without an active site base: a unifying mechanism for Ras and related GTPases

AR Calixto, C Moreira, A Pabis, C Kötting… - Journal of the …, 2019 - ACS Publications
GTP hydrolysis is a biologically crucial reaction, being involved in regulating almost all
cellular processes. As a result, the enzymes that catalyze this reaction are among the most …

Ras and GTPase-activating protein (GAP) drive GTP into a precatalytic state as revealed by combining FTIR and biomolecular simulations

T Rudack, F **a, J Schlitter… - Proceedings of the …, 2012 - National Acad Sciences
Members of the Ras superfamily regulate many cellular processes. They are down-
regulated by a GTPase reaction in which GTP is cleaved into GDP and P i by nucleophilic …

Hydrolysis of guanosine triphosphate (GTP) by the Ras· GAP protein complex: reaction mechanism and kinetic scheme

MG Khrenova, BL Grigorenko… - The Journal of …, 2015 - ACS Publications
Molecular mechanisms of the hydrolysis of guanosine triphosphate (GTP) to guanosine
diphosphate (GDP) and inorganic phosphate (Pi) by the Ras· GAP protein complex are fully …

Identification of functional substates of KRas during GTP hydrolysis with enhanced sampling simulations

J Zeng, J Chen, F **a, Q Cui, X Deng… - Physical Chemistry …, 2022 - pubs.rsc.org
As the hub of major signaling pathways, Ras proteins are implicated in 19% of tumor-caused
cancers due to perturbations in their conformational and/or catalytic properties. Despite …