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The Ras superfamily of small GTPases are important intracellular signaling molecules, the functions of which are determined by the binding of guanosine nucleotides (GTP= guanosine triphosphate and GDP= guanosine diphosphate).[1] The GTP-bound (“active”) states of these enzymes are capable of interacting with specific downstream effector proteins, thus eliciting a wide range of cellular responses.[2, 3] Mutations that reduce the rate of GTP hydrolysis and thus increase the lifetime of the active GTP-bound state are frequently oncogenic and contribute to the development and metastasis of human cancers.[4] Elegant 31P NMR studies of GTP-bound Ras showed that the enzyme interconverts between two states, a minor conformer termed state 1 and a major species designated state 2.[5–9] Similar conformational dynamics have been observed in other Ras family GTPases as well.[10–12] State 2 is generally regarded as the conformation competent for binding effector proteins, whereas state1 exhibits significantly reduced affinity for these molecules.[5–7, 13, 14] Stabilization of the low-affinity state1 was hence suggested as a strategy to inhibit Ras–effector interactions so as to reduce oncogenic signaling.[15–17] For example, Zn2+–bis (2-picolyl) amine complexes [18] were found to stabilize state 1 and inhibit Ras–effector interactions by binding to an allosteric site, albeit with low (millimolar) affinity. The intrinsic GTPase activity of Ras leads to the conversion of Ras· GTP to Ras· GDP within a few hours at room temperature, imposing a practical limit on the duration of experiments that can be performed with physiological GTP. For this reason …