Computational study of a transition state analog of phosphoryl transfer in the Ras-RasGAP complex: AlFx versus MgF3

The structures of the complexes between Ras.GDP bound to RasGAP in the presence of three probable g-phosphate analogs (AlF3433, AlF- and MgF-) 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., AlF (or MgF)(-). 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 MgF)(3)(3)- is the most likely candidate for the phosphate analog in the experimental structure

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