RASA1 Ras GAP - 3D Mechanism Simulator

Loading structural data… (1WQ1)

References & Databases

START HERE — how to read Ras·GTP + H₂O → Ras·GDP + Pi (GAP-stimulated) A single GAP-stimulated hydrolysis cartoon on the human p120GAP frame that exists: 1WQ1 (2.50 Å), GAP chain G, catalytic H-Ras R with GDP, AlF₃, and Mg. AlF₃ is a named occupancy analog of γ-P, not GTP. GDP is crystal. Pi and water are [schematic]. Arg789 is the GAP arginine finger. The GAP is not the hydrolase — Ras is. No EC. NF1 is another gene. KRAS/NRAS are other genes. Oncogenic G12/Q61 are Regulation, not motion. A-page (no covalent E~P).
Crystal structures PDB 1WQ1 — human p120GAP·H-Ras·GDP·AlF₃·Mg, 2.50 Å (Scheffzek 1997). Coordinates are public. AF3 sits at the γ-P analog seat. GDP is deposited. NF1 structures are other genes. HRAS and SOS1 are other pages on this path, not this mesh.
Mechanism — Arg finger, Ras hydrolyses, GAP is not the hydrolase Scheffzek et al., Science 1997, PMID:9219684 — Ras–RasGAP complex, structural basis for GTPase activation. UniProt P20936 GAP. Crystal analog is AlF₃, not GTP. Product is Ras·GDP (switch off). Physiological nucleotide teaching = GTP hydrolysed — analog occupancy, not this mesh. The GAP is not the hydrolase; Ras is. Source: Scheffzek 1997 · UniProt P20936
0 — Setup: empty analog cleft 1WQ1 holds p120GAP, H-Ras, GDP, AlF₃, and Mg. The pocket starts empty so the analog can dock. Opaque, no autoplay. Chemistry below uses crystal AlF₃ as a named stand-in for γ-P. GAP, not a hydrolase EC. No EC.Source: PDB 1WQ1
① — GDP·AlF₃·Mg presented Crystal GDP docks with AlF₃ and Mg as a named stand-in for the GTP-hydrolysis analog — [schematic occupancy], not GTP. AlF₃ stands in for γ-P. GDP O3B ⋯ AL = 2.29 Å; GDP O2B ⋯ MG = 1.85 Å; Ser17 OG ⋯ MG = 2.00 Å on this deposit. Overlay water Å are not geomClaims.Source: 1WQ1 GDP + AF3 + MG pose
② — Arg789 finger contacts AlF₃ (hypothetical, lit.-based) The GAP arginine finger (Arg789 ★) contacts analog F3. The protein mesh is static. The GAP is not the hydrolase; Ras is. Arg789 NH1 ⋯ F3 = 2.60 Å on this deposit. Slow-motion on purpose. NF1 is another gene.Source: compiled GAP Arg finger · Scheffzek 1997 PMID:9219684
③ — OH⁻ attacks analog γ-P → GDP + Pi (hypothetical, lit.-based) The OH⁻ itself (the water O) rides onto the analog Al in slow motion and becomes the new Pi oxygen — the moving ball is the nucleophile, not a separate marker. AlF₃ fades in place to schematic Pi. Crystal GDP stays. Water is consumed. Overlay water Å are not geomClaims. Slow-motion on purpose. A-page. AlF₃ ≠ GTP. The GAP is not the hydrolase.Source: compiled GAP-stimulated GTPase · UniProt P20936
④ — Pi leaves (hypothetical, lit.-based) Schematic Pi departs. GDP and Mg stay. Teaching = GTP hydrolysed with GAP help. AlF₃ was occupancy, not this chemistry.Source: GAP-stimulated net accounting
⑤ — GDP·Mg leaves — GAP-stimulated switch off [schematic leave of crystal ligands] GDP and Mg depart opposite Pi. The product is H-Ras·GDP — switch off, GAP-stimulated. AlF₃ ≠ GTP. NF1 is another gene. KRAS/NRAS are other genes. Oncogenic G12/Q61 are Regulation, not this motion.Source: GAP-stimulated net accounting · UniProt P20936

How to read this page — a first-pass primer First pass: Setup (empty analog cleft, Arg789 ★) → ① GDP·AlF₃·Mg docks → ② Arg finger contacts F3 → ③ the OH⁻ itself rides onto the Al, analog becomes Pi → ④ Pi leaves → ⑤ GDP·Mg leave; switch off. Second pass: 1.85 / 2.00 / 2.29 / 2.60 Å are crystal facts on 1WQ1; Pi, water, and nucleophile spheres are [schematic]. Third pass: open “Disagreements” for AlF₃ ≠ GTP, GAP not hydrolase, no EC, NF1, and G12/Q61 as Regulation.
Chemistry primer — GAP accelerates Ras, is not the hydrolase RASA1 (p120GAP) accelerates H-Ras GTP hydrolysis. The hydrolase is Ras, not the GAP. Gold H⁺ is not drawn as a parked Gln61 event on this page — the teaching beat is the Arg finger. Blue = water-OH nucleophile (not hydride). Product is Ras·GDP — switch off. This is not SOS1 nucleotide exchange, and not the unstimulated HRAS page.
Words used on screen — occupancy · analog · Arg finger · NF1 Occupancy — AlF₃ is the crystal analog of γ-P; never relabeled as GTP. Analog — AlF₃ + GDP stand in for the GTP-hydrolysis transition-state mimic. Arg finger — GAP Arg789 that contacts analog F3. NF1 — other gene. PDB numbering = UniProt P20936 718–1037 on GAP; H-Ras 1–166.

Legend & Fidelity

Mechanism fidelity — measured vs. inferred The measured layer: 1WQ1 (2.50 Å) with GDP, AlF₃, and Mg; GDP O2B ⋯ MG = 1.85 Å; Ser17 OG ⋯ MG = 2.00 Å; GDP O3B ⋯ AL = 2.29 Å; Arg789 NH1 ⋯ F3 = 2.60 Å. The inferred layer ([schematic]): Pi, water, transferring nucleophile sphere, product leave, and Arg-finger label as motion. Binding order is compiled staging, not a kinetic fit. The protein mesh is static. Overlay water contacts are not geomClaims. Gln61 is compiled and far from AL on this pose.
Disagreements on record (a) AlF₃ ≠ GTP. AF3 is occupancy analog of γ-P. (b) GAP is not the hydrolase. Ras is. No EC. Do not invent 3.6.5.2 on RASA1. (c) Gln61 is far from AL on this pose. Compiled water-orienting residue; not a geomClaim. (d) NF1 is another gene. (e) Oncogenic G12 / Q61 are Regulation, not motion. (f) No protein-domain swing. Arg finger does not morph. (g) KRAS / NRAS are other genes. (h) GEF is the SOS1 page, not this mesh.
Regulation — oncogenic G12/Q61 · isoforms · NF1 Oncogenic G12 / Q61 impair GAP-stimulated hydrolysis — named on this page, not animated as mutant motion. NF1 is another gene. KRAS / NRAS are other genes. SOS1 (GEF) and HRAS (unstimulated GTPase) are other pages on this path.Source: UniProt P20936 · Scheffzek 1997 PMID:9219684
Kinetics scope (no measured timecourse on this page) One Ras·GTP + H₂O → Ras·GDP + Pi event is drawn, not a steady-state run. Compiled GAP-stimulated rates are not re-asserted here — no measured k_cat/K_m on this page [schematic]. Pair with a kinetics chapter. This page has no EC number.Source: UniProt P20936 — no k_cat/K_m re-asserted
Sequence Human RASA1 UniProt P20936 · NCBI Gene 5921. Screen uses 1WQ1 PDB-author numbering (GAP 718–1037 = UniProt; H-Ras 1–166). NF1 is another gene. KRAS / NRAS are other genes.
Simulation map — what you see is what is written Setup = 1WQ1 empty analog cleft (opaque, no autoplay). ① GDP·AlF₃·Mg moves in (crystal occupancy). ② slow-mo Arg-finger label on a static protein. ③ slow-mo: the OH⁻ itself glides in and rides onto the Al, becoming a Pi oxygen; analog fades to Pi. ④ Pi leaves. ⑤ GDP·Mg leave; switch off. Only these events move.
Sources — bibliography of this page S1 — PDB 1WQ1: human p120GAP·H-Ras·GDP·AF3·MG, 2.50 Å — public coordinates; measured O2B⋯MG = 1.85 Å · OG⋯MG = 2.00 Å · O3B⋯AL = 2.29 Å · NH1⋯F3 = 2.60 Å S2 — Scheffzek et al., Science 1997, PMID:9219684 — Ras–RasGAP complex, structural basis for GTPase activation S3 — Sequence: UniProt P20936 (human RASA1) · NCBI Gene 5921 S4 — Kinetics: UniProt P20936 — no EC; no k_cat/K_m re-asserted on this page

› Backbones and ligand poses are taken directly from the listed PDB entries, superposed into one common frame. Where no crystalline state exists for a step (e.g., GTP identity, Pi after hydrolysis, H⁺ flight, product release), the pose is drawn schematically and labeled as such in the narration.

p120GAPH-RasONnucleophile (blue)