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Updated: Aug 16, 2026

Comparing the Affinity of GTPase-binding Proteins using Competition Assays
Published on: October 8, 2015
Computational study of a transition state analog of phosphoryl transfer in the Ras-RasGAP complex: AlF(x) versus
Bella L Grigorenko1, Alexander V Nemukhin, Raul E Cachau
1Department of Chemistry, M. V. Lomonosov Moscow State University, Moscow, 119992, Russian Federation.
Abstract:
The structures of the complexes between Ras*GDP bound to RasGAP in the presence of three probable gamma-phosphate analogs (AlF3, AlF4- and MgF3-) for the transition state (TS) of the hydrolysis of guanosine triphosphate (GTP) by the Ras-RasGAP enzymes have been modeled by quantum mechanical-molecular mechanical (QM/MM) calculations. These simulations contribute to the dispute on the nature of the TS in the hydrolysis reaction, since medium resolution X-ray crystallography cannot discern among stereochemically similar isoelectronic species (e.g., AlF3 or MgF3-). The optimized geometry for each structure has been found starting from experimental coordinates of one of them (PDBID: 1WQ1). Direct comparison of the experimental and computed geometry configurations in the immediate vicinity of the active site suggests that MgF3- is the most likely candidate for the phosphate analog in the experimental structure.
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