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Cited by 4 publications
(4 citation statements)
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References 7 publications
(10 reference statements)
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“…These observations suggest that the interactions of Ca(OAc) 2 with residues in helix α3, loop L7, and helix α4 trigger conformational changes in the allosteric lobe of H-Ras that can transmit to the effector lobe to order the switch II region. 241 Under these circumstances, the catalytic residue Q61 in the ordered switch II region can interact with the bridging water molecule (W189), which in turn interacts with the side chain of Y32 and γ-phosphate (Figure 26C), rendering the H-Ras−GTP in its precatalytic conformation at the beginning of the hydrolysis reaction. In this context, the H-Ras WT −GppNHp−Ca(OAc) 2 structure represents a catalytically competent state ("on" conformation), while the H-Ras WT −GppNHp−CaCl 2 structure represents a catalytically incompetent state ("off" conformation).…”
Section: Allosteric Switch Of Ras−gtp To the Onmentioning
confidence: 99%
See 1 more Smart Citation
“…These observations suggest that the interactions of Ca(OAc) 2 with residues in helix α3, loop L7, and helix α4 trigger conformational changes in the allosteric lobe of H-Ras that can transmit to the effector lobe to order the switch II region. 241 Under these circumstances, the catalytic residue Q61 in the ordered switch II region can interact with the bridging water molecule (W189), which in turn interacts with the side chain of Y32 and γ-phosphate (Figure 26C), rendering the H-Ras−GTP in its precatalytic conformation at the beginning of the hydrolysis reaction. In this context, the H-Ras WT −GppNHp−Ca(OAc) 2 structure represents a catalytically competent state ("on" conformation), while the H-Ras WT −GppNHp−CaCl 2 structure represents a catalytically incompetent state ("off" conformation).…”
Section: Allosteric Switch Of Ras−gtp To the Onmentioning
confidence: 99%
“…In addition, the two oxygen atoms of acetate form hydrogen bonds with the side chain of R97 on helix α3 and the backbone NH group of V109 on loop L7, respectively. These observations suggest that the interactions of Ca­(OAc) 2 with residues in helix α3, loop L7, and helix α4 trigger conformational changes in the allosteric lobe of H-Ras that can transmit to the effector lobe to order the switch II region . Under these circumstances, the catalytic residue Q61 in the ordered switch II region can interact with the bridging water molecule (W189), which in turn interacts with the side chain of Y32 and γ-phosphate (Figure C), rendering the H-Ras–GTP in its precatalytic conformation at the beginning of the hydrolysis reaction.…”
Section: Allosteric Switch Of Ras–gtp To the On Statementioning
confidence: 99%
“…Ras often functions at downstream of Src and exists in two conformations: a GTP-bound active state and GDPbound inactive state. Ratios of GTP-and GDP-bound Ras are controlled by guanine nucleotide exchange proteins and GTPase-activating proteins, the activity of which responds to activation of extracellular (such as growth factors) or intracellular receptors (like Src) [19][20][21][22]. Once interacting with the effectors, signals generated from Ras influence cell growth, migration and other activities.…”
Section: Introductionmentioning
confidence: 99%
“…Given their central role in oncogenesis, RAS has been spotlighted as an intriguing target for anticancer drug development, and the inhibition of RAS proteins has been considered a promising direction in oncology 17 , 18 , 26 , 27 , 28 . However, many failures occur in the earlier exploration, in large part ascribed to the picomolar affinity of RAS for guanine nucleotide and lack of deep hydrophobic pockets amenable for small molecule ligands, leading to an ‘undruggable’ portrait of RAS 3 , 18 .…”
Section: Introductionmentioning
confidence: 99%