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How converging fingers keep GTP in line

The figure here shows a simplified view of how arginine fingers stabilize the GTPase-reaction transition state. Depicted are the GDP (grey), AlF4 (a red aluminium surrounded by four yellow fluorine atoms), the attacking water (grey) and the conserved glutamine residue (magenta) as seen in the GDP.AlF4-bound structure of the Gαi1–RGS4 complex1.

In the three distinct GTP-hydrolysing machines1,2,3 discussed in the main text b arginine fingers converge on the same point b stabilizing γ bphosphate oxygens and the leaving group. The finger pointed in cis by Gαi1(green) approaches from one direction, while arginines supplied by RasGAP (blue) and RhoGAP (cyan) point from the opposite direction. AlF3, which was found in the Ras-RasGAP structure2, presumably mimics the transition state more accurately than does the AlF4 shown here, which was seen in the Gαi1-RGS4 and RhoA-RhoGAP crystals1,3.

The transition state is bipyramidal, with a central phosphorus (the Al3+ ion in crystals) located equidistant from the leaving group (an oxygen of GDP's β-phosphate) and an attacking water molecule, which is destined to donate an oxygen to form a product of the GTPase reaction, inorganic phosphate. A straight line (black dots), perpendicular to the plane formed by the phosphorus and its three oxygens, connects the leaving group, phosphorus and water. The position of every atom in the transition state is stabilized by a network of hydrogen bonds connecting it to a Mg2+ ion and/or neighbouring amino acids from the GTP-binding protein. This network is omitted here, except for bonds involving the arginine of Gαi1and bonds connecting the glutamine to the water and AlF4. In addition, arginine ‘knuckles’ (main-chain carbonyls) positioned by the GAPs stabilize the amide group of the glutamine's side chain; this stabilizing influence is represented by an imaginary bond connecting the arginine main chain of RhoGAP to the glutamine of Gαi1. (Coordinates of crystal structures kindly provided by S. Sprang1, A. Wittinghofer2 and S. J. Smerdon3. Elaine Meng helped in making the graphic.)

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Bourne, H. How converging fingers keep GTP in line. Nature 389, 674 (1997). https://doi.org/10.1038/39472

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