GTPase HRas - 3D Mechanism Simulator

Loading structural data… (5P21)

References & Databases

START HERE — how to read GTP + H₂O → GDP + Pi A single nucleotide-switch cartoon on the human H-Ras frame that exists: 5P21 (1.35 Å), chain A, with GppNp (GNP) and Mg. That analog is a named occupancy, not GTP — the bridge is N3B, not O3B. GDP, Pi, and water are [schematic]. Gln61 orients water (compiled; far on this pose). Gold H⁺ parks on Gln61; blue is the water-OH nucleophile, not a hydride. Overlay water distances are not geomClaims. KRAS/NRAS are other genes. Oncogenic G12/Q61 are Regulation, not motion. A-page (no covalent E~P).
Crystal structures PDB 5P21 — human H-Ras·GppNp·Mg, 1.35 Å (Pai 1990). Coordinates are public. KRAS / NRAS structures are other genes. SOS1 and RASA1 are later pages on this path, not this mesh.
Mechanism — Gln61 orients water, OH⁻ attacks γ-P Pai et al., EMBO J 1990, PMID:2196171 — refined 1.35 Å triphosphate conformation of H-ras p21. UniProt P01112 GTPase. Crystal ligand is GppNp, not GTP. Product is Ras·GDP (switch off). Physiological nucleotide teaching = GTP — analog occupancy, not this mesh. Source: Pai 1990 · UniProt P01112
0 — Setup: empty nucleotide cleft 5P21 holds H-Ras, GppNp, and Mg. The pocket starts empty so the analog can dock. Opaque, no autoplay. Chemistry below uses crystal GppNp as a named stand-in for GTP.Source: PDB 5P21
① — GppNp·Mg presented Crystal GppNp docks with Mg as a named stand-in for GTP — [schematic occupancy], not GTP. The bridge atom is nitrogen (N3B), not oxygen. GNP O2G ⋯ MG = 2.20 Å; Ser17 OG ⋯ MG = 2.26 Å on this deposit. Overlay water Å are not geomClaims.Source: 5P21 GNP + MG pose
② — Gln61 orients water (hypothetical, lit.-based) A schematic water glides in to the γ-P face (it is not popped into place). Gold H⁺ leaves water H2 toward Gln61 NE2 and parks. Remaining OH⁻ is the nucleophile. On this 5P21 pose Gln61 is far from PG — not a geomClaim. Oncogenic Q61 is Regulation, not this motion.Source: compiled GTPase water orientation · UniProt P01112
③ — Water-OH attacks γ-P → GDP + Pi (hypothetical, lit.-based) The OH⁻ itself (the water O) rides onto the analog PG in slow motion and becomes the new Pi oxygen — the moving ball is the nucleophile, not a separate marker. GppNp fades in place to schematic GDP + Pi. Water is consumed. Parked gold H⁺ stays on Gln61. Overlay water Å are not geomClaims. Slow-motion on purpose. A-page. GppNp ≠ GTP.Source: compiled GTPase hydrolysis · UniProt P01112
④ — Pi leaves (hypothetical, lit.-based) Schematic Pi departs. GDP and Mg stay. Teaching = GTP hydrolysed. GppNp was occupancy, not this chemistry.Source: EC 3.6.5.2 net accounting
⑤ — GDP·Mg leaves — switch off [schematic] GDP and crystal Mg depart opposite Pi. The product is H-Ras·GDP — switch off. GppNp ≠ GTP. KRAS/NRAS are other genes. Oncogenic G12/Q61 are Regulation, not this motion.Source: EC 3.6.5.2 net accounting

How to read this page — a first-pass primer First pass: Setup (empty cleft, Gln61 ★) → ① GppNp·Mg docks → ② gold H⁺ parks on Gln61 → ③ blue OH → PG, analog becomes GDP + Pi → ④ Pi leaves → ⑤ GDP·Mg leave; switch off. Second pass: 2.20 / 2.26 / 2.68 / 3.25 Å are crystal facts on 5P21; GDP, Pi, water, and H spheres are [schematic]. Third pass: open “Disagreements” for GppNp ≠ GTP, Gln61 far, KRAS/NRAS, and G12/Q61 as Regulation.
Chemistry primer — GTPase switch, not a kinase H-Ras hydrolyses GTP to GDP + Pi. Gold = H⁺. Blue = water-OH nucleophile (not hydride). Product is Ras·GDP — switch off. This is not SOS1 nucleotide exchange, and not RASA1 GAP acceleration. A-page: no covalent E~P.
Words used on screen — occupancy · analog · switch · KRAS Occupancy — GppNp is the crystal ligand; never relabeled as GTP. Analog — GppNp is a non-hydrolysable stand-in (N3B ≠ O3B). Switch — GTP-bound on, GDP-bound off. KRAS / NRAS — other genes. PDB numbering = UniProt P01112 1–166.

Legend & Fidelity

Mechanism fidelity — measured vs. inferred The measured layer: 5P21 (1.35 Å) with GppNp and Mg; GNP O2G ⋯ MG = 2.20 Å; Ser17 OG ⋯ MG = 2.26 Å; Lys16 NZ ⋯ O3G = 2.68 Å; PG ⋯ MG = 3.25 Å. The inferred layer ([schematic]): GDP, Pi, water, transferring H⁺/nucleophile spheres, product leave, and deprotonation/attack split. 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 on this pose.
Disagreements on record (a) GppNp ≠ GTP. GNP is occupancy (N3B ≠ O3B). (b) Gln61 is far on this pose. Compiled water-orienting residue; not a geomClaim. (c) Deprotonation vs attack split. Compiled GTPase writes them as one event; this page plays two beats. (d) KRAS / NRAS are other genes. (e) Oncogenic G12 / Q61 are Regulation, not motion. (f) No protein-domain swing. Switch I/II do not morph. (g) GAP / GEF are later pages, not this mesh.
Regulation — oncogenic G12/Q61 · isoforms · GAP/GEF Oncogenic G12 / Q61 impair hydrolysis — named on this page, not animated as mutant motion. KRAS / NRAS are other genes. SOS1 (GEF) and RASA1 (GAP) accelerate nucleotide exchange / hydrolysis on later pages of this path.Source: UniProt P01112 · Pai 1990 PMID:2196171
Kinetics scope (no measured timecourse on this page) One GTP + H₂O → GDP + Pi event is drawn, not a steady-state run. Compiled BRENDA values for EC 3.6.5.2 are not re-asserted here — no measured k_cat/K_m on this page [schematic]. Pair with a kinetics chapter.Source: BRENDA EC 3.6.5.2 — no k_cat/K_m re-asserted
Sequence Human HRAS UniProt P01112 · NCBI Gene 3265. Screen uses 5P21 PDB-author numbering (1–166 = UniProt). KRAS / NRAS are other genes.
Simulation map — what you see is what is written Setup = 5P21 empty nucleotide cleft (opaque, no autoplay). ① GppNp·Mg moves in (crystal occupancy). ② the water glides in, then gold H⁺ parks on Gln61. ③ slow-mo: the OH⁻ itself rides onto PG and becomes the Pi oxygen; analog fades to GDP + Pi. ④ Pi leaves. ⑤ GDP·Mg leave; switch off. Only these events move.
Sources — bibliography of this page S1 — PDB 5P21: human H-Ras·GppNp·MG, 1.35 Å — public coordinates; measured O2G⋯MG = 2.20 Å · OG⋯MG = 2.26 Å · NZ⋯O3G = 2.68 Å · PG⋯MG = 3.25 Å S2 — Pai et al., EMBO J 1990, PMID:2196171 — refined 1.35 Å triphosphate conformation of H-ras p21 S3 — Sequence: UniProt P01112 (human HRAS) · NCBI Gene 3265 S4 — Kinetics: BRENDA EC 3.6.5.2 — 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, GDP/Pi after hydrolysis, H⁺ flight, product release), the pose is drawn schematically and labeled as such in the narration.

H-RasONH⁺ (gold)nucleophile (blue)