The five machines
HRas (small GTPase)
GTP + H₂O → GDP + Pᵢ
The switch itself. Intrinsic GTP hydrolysis turns it off (slowly, on its own). Gln61 and the P-loop orient the attacking water.
EC 3.6.5.2 · PDB 5P21
▶ OPEN SIMULATORSOS1 (guanine-nucleotide exchange factor)
Ras·GDP + GTP ⇌ Ras·GTP + GDP
Pries GDP out so the abundant GTP can take its place — switches Ras on. It does not hydrolyse anything; it destabilizes the nucleotide site.
GEF (no EC hydrolase) · PDB 1NVV
▶ OPEN SIMULATORRASA1 (p120 RasGAP)
Ras·GTP + H₂O → Ras·GDP + Pᵢ
Accelerates Ras's own hydrolysis by orders of magnitude: its Arg finger stabilizes the transition state. Same reaction as HRas, faster.
GAP · PDB 1WQ1
▶ OPEN SIMULATORPI3Kα (PIK3CA catalytic subunit)
PIP₂ + ATP → PIP₃ + ADP
Recruited by active Ras·GTP. Phosphorylates the membrane lipid PIP₂ at the 3-OH to make PIP₃ — a docking signal. PI3K appears only on this page.
EC 2.7.1.137 · PDB 2RD0
▶ OPEN SIMULATORPTEN (PIP₃ 3-phosphatase)
PIP₃ + H₂O → PIP₂ + Pᵢ
The brake on the same signal: removes the 3-phosphate from PIP₃, undoing PI3K. A Cys phosphatase with a metal-assisted water.
EC 3.1.3.67 · PDB 1D5R
▶ OPEN SIMULATOR