Glucose-6-phosphatase - 3D Mechanism Simulator

Loading structural data… (9JTM)

References & Databases

START HERE — how to read G6P + H₂O → glucose + Pi A histidine-phosphatase cartoon on the human G6PC1 frame that actually exists: 9JTM (2.90 Å) is an H176N trap with G6P bound. WT nucleophile is His176 from a 9JTN overlay (Cα RMSD 1.76 Å), not Ser176. His119 is the leaving-group proton donor. Covalent E~P is drawn — this is not a pure A-page. P5S is a named membrane lipid. Glucose / Pi / water / E~P geometry is [schematic]. Overlay His176 NE2⋯P is not a geomClaim.
Crystal structures PDB 9JTM — human G6PC1 H176N + G6P, 2.90 Å (Chen 2025). Coordinates are public. SEQADV: residue 176 is ASN (engineered). PDB 9JTN supplies the WT His176 overlay only (3.10 Å EM + PO4). Plan-line Ser176 is discarded — the deposit is His176.
Mechanism — His176 E~P then water UniProt P35575 EC 3.1.3.9: G6P + H₂O → glucose + Pi. Chen et al. 2025, PMID:40664655 — 9JTM/9JTN. Overlay His176 attacks P; glucose leaves; water hydrolyses E~P. Overlay contacts are not geomClaims. Source: UniProt P35575 · Chen 2025
0 — Setup: H176N trap, pocket shown empty 9JTM holds G6P and P5S. The pocket is shown empty so ordered binding can start. P5S stays as a named membrane-lipid occupant. Opaque, run:null (no autoplay). Asn176 is the trap, not the nucleophile.Source: PDB 9JTM
① — G6P binds (crystal) Deposited G6P A701 docks. Arg83 NH1 ⋯ O3P = 2.91 Å. The mesh is H176N — Asn176 ND2 ⋯ O1P = 2.91 Å is a trap contact, not WT chemistry.Source: 9JTM G6P A701
② — His176 attacks P → E~P (hypothetical, lit.-based) Overlay His176 ★ (blue arrow = nucleophile, not a hydride) attacks phosphorus. G6P fades to schematic glucose + covalent E~P. 9JTN overlay, not a WT ternary on this mesh. Slow-motion on purpose.Source: histidine phosphatase · 9JTN overlay
③ — Glucose leaves (hypothetical, lit.-based) Schematic glucose departs. E~P stays on His176. His119 was the leaving-group proton donor (ND1 ⋯ O6 = 3.28 Å).Source: EC 3.1.3.9 ping-pong
④ — Catalytic water binds Water slides toward E~P — [schematic]. 9JTM waters 801–803 are deposited but not extracted as this nucleophile seat.Source: compiled hydrolase water
⑤ — Water hydrolyses E~P → Pi (hypothetical, lit.-based) Gold H⁺ leaves water H2. Remaining OH⁻ attacks E~P. E~P fades to schematic Pi at the His176 seat (fourth O = water; O6 stayed on glucose). Water consumed.Source: E~P hydrolysis
⑥ — Pi leaves — free glucose is the GNG product Schematic Pi departs. P5S stays. Free glucose leaves the ER. von Gierke (G6PC1) alleles are not this motion.Source: GNG bookkeeping

How to read this page — a first-pass primer First pass: Setup (H176N trap, pocket empty, P5S stays) → ① crystal G6P docks → ② overlay His176 attacks P, G6P becomes glucose + E~P → ③ glucose leaves → ④ water docks → ⑤ gold H⁺ leaves water, E~P becomes Pi → ⑥ Pi leaves. Second pass: 2.91 Å is a crystal fact on 9JTM; His176 and E~P are overlay / [schematic]. Third pass: open “Disagreements” for H176N vs WT, Ser176 discarded, and covalent E~P.
Chemistry primer — histidine phosphatase G6Pase is an ER-membrane histidine phosphatase. His176 forms a covalent E~P; glucose leaves; water hydrolyses E~P to Pi. Gold = H⁺. Blue on this page = His176 / OH⁻ nucleophile, not hydride. Net: G6P + H₂O → glucose + Pi. Not a metal-OH A-page like FBPase.
Words used on screen — H176N trap · overlay His176 · P5S lipid H176N trap — 9JTM engineers Asn at 176 so G6P cannot transfer. Overlay His176 — 9JTN WT histidine Kabsch-fit onto 9JTM, not a WT ternary. P5S lipid — deposited membrane lipid occupant, not the substrate.

Legend & Fidelity

Mechanism fidelity — measured vs. inferred The measured layer: 9JTM (2.90 Å) with G6P A701 and P5S; Arg83 / Arg170 / His119 / Lys76 / Gly118 / Asn176 contacts. The inferred layer ([schematic]): overlay His176, transferring H⁺/OH⁻, E~P (NEP), glucose, Pi, water seat, product leave. Binding order is compiled staging, not a kinetic fit. The protein mesh is static. Overlay contacts are not geomClaims.
Disagreements on record (a) H176N is not WT. 9JTM cannot show His176 chemistry. (b) Ser176 is discarded. An early plan line named Ser176; the deposit is His176 (9JTN) / Asn176 (9JTM). (c) Overlay ≠ WT ternary. 9JTN onto 9JTM (RMSD 1.76 Å). (d) E~P is covalent — not a pure A-page. (e) Water seat is schematic. Deposited HOH 801–803 are not this nucleophile. (f) Split vs compiled. Compiled G6Pase writes E~P formation then hydrolysis; this page also splits glucose leave and water-in.
Regulation — ER lumen · G6PC1 vs G6PC3 · von Gierke G6PC1 is the liver/kidney/intestine catalytic subunit in the ER membrane. Glucose-6-phosphate enters via SLC37A4 (G6PT). G6PC3 is a different gene (ubiquitous, severe congenital neutropenia) — not this mesh. Biallelic G6PC1 alleles cause glycogen storage disease Ia (von Gierke) — named, not simulated.Source: UniProt P35575 · GSD Ia
Kinetics scope (no measured timecourse on this page) One G6P → glucose event is drawn, not a steady-state run. Compiled BRENDA values for EC 3.1.3.9 are not re-asserted here — no measured k_cat/K_m on this page [schematic]. Pair with a kinetics chapter.Source: BRENDA EC 3.1.3.9 — no k_cat/K_m re-asserted
Sequence Human G6PC1 UniProt P35575 · NCBI Gene 2538. Screen uses 9JTM numbering. Cα 1–351; gap 142–146. Overlay His176 is 9JTN onto this mesh.
Simulation map — what you see is what is written Setup = 9JTM pocket empty, P5S visible (opaque, run:null). ① crystal G6P moves in. ② slow-mo: blue His176 attacks P; G6P fades to glucose + E~P. ③ glucose leaves; E~P stays. ④ schematic water moves in. ⑤ gold H⁺ leaves water H2; E~P fades to Pi; water consumed. ⑥ Pi leaves; P5S stays. Only these events move.
Sources — bibliography of this page S1 — PDB 9JTM: human G6PC1 H176N + G6P, 2.90 Å — public coordinates; measured NH1⋯O3P = 2.91 Å S2 — PDB 9JTN: WT His176 overlay onto 9JTM (Cα RMSD 1.76 Å) — [schematic] nucleophile, not a WT ternary S3 — Chen et al. 2025, PMID:40664655 — 9JTM / 9JTN S4 — Sequence: UniProt P35575 (human G6PC1) · NCBI Gene 2538 S5 — Kinetics: BRENDA EC 3.1.3.9 — 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., overlay His176 identity, E~P, water seat, OH⁻ flight, product release), the pose is drawn schematically and labeled as such in the narration.

N-lobeC-lobeONH⁺ (gold)nucleophile (blue)