6-Phosphogluconate Dehydrogenase - 3D Mechanism Simulator

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References & Databases

START HERE — how to read 6PG + NADP⁺ → Ru5P + CO₂ + NADPH + H⁺ A single oxidative-decarboxylation cartoon on the human PGD pocket. Real crystal: 2JKV (2.53 Å) with NADPH (NAP A500). 6PG is not in 2JKV — the sugar, 3-keto, enediol, Ru5P and CO₂ are [schematic]. The pocket is an A·B dimer interface: Lys184B ★ (UniProt proton acceptor) and Glu191B ★ (UniProt proton donor) come from the partner subunit. Same-chain Lys184A is ~42 Å away and is the wrong residue. Hydride donor is 6PG C3 to nicotinamide C4. Gold H⁺ parks on Lys184B; blue H⁻ is the hydride. Schematic contacts are not geomClaims.
Crystal structures PDB 2JKV — human 6-phosphogluconate dehydrogenase + NADPH, 2.53 Å (SGC / Ng et al.). Coordinates are public. There is no deposited 6PG ternary on this frame. 4GWG (apo) is not this mesh.
Mechanism — Lys184B base, C3 hydride, decarboxylation, Glu191B tautomer UniProt P52209 ACT_SITE: Lys184 proton acceptor, Glu191 proton donor. Hydride leaves 6PG C3 for NADP C4; the 3-keto decarboxylates to an enediol + CO₂; Glu191 tautomerizes the enediol to ribulose 5-phosphate (Rhea 10116). Net: 6PG + NADP⁺ → Ru5P + CO₂ + NADPH + H⁺ — one H⁺, the same count as G6PD. Source: UniProt P52209 · PDB 2JKV · Rhea 10116
0 — Setup: NADPH crystal, catalytic pocket shown empty 2JKV holds NADPH (NAP A500). The catalytic pocket is shown empty so ordered binding can start. Opaque, run:null (no autoplay). Lys184B ★ / Glu191B ★ sit on the dimer interface. 6PG is not in this crystal.Source: PDB 2JKV
① — NADP⁺ binds (reaction state · NAP A500 = deposited NADPH) Crystal NAP docks as the oxidized reaction state (2JKV deposits A500 as NADPH). Nicotinamide C4 is the hydride acceptor. Lys184B NZ ⋯ C4N = 4.84 Å on this binary (measured on 2JKV; no 6PG in the deposit). NADP-first order is compiled staging, not a fit.Source: 2JKV NAP A500 pose
② — 6PG binds (schematic) 6PG is seated on the 2JKV mesh — [schematic], not a ternary. C3-OH faces Lys184B. Schematic contacts are teaching geometry, not geomClaims.Source: compiled 6PGDH C3-OH geometry
③ — Lys184B ★ abstracts the C3-OH proton (hypothetical, lit.-based) A gold H⁺ sphere rides a gold arrow from 6PG O3 to Lys184B NZ and parks. The alkoxide label is a teaching overlay. Compiled 6PGDH writes this proton transfer with the hydride; this page splits them.Source: UniProt P52209 ACT_SITE Lys184 acceptor
④ — Hydride C3 → NADP⁺ C4 → 3-keto-6PG + NADPH (hypothetical, lit.-based) Blue H⁻ (hydride) rides from 6PG C3 to NADP C4N. 6PG fades in place to schematic 3-keto-6PG; NADP⁺ relabels NADPH. Parked gold H⁺ stays on Lys184B. Schematic C3⋯C4N is not a measured hydride Å. Slow-motion on purpose.Source: compiled 6PGDH C3→C4
⑤ — Decarboxylation → enediol + CO₂ (hypothetical, lit.-based) The 3-keto decarboxylates at C1. Schematic CO₂ is born at the carboxylate and leaves. The remaining skeleton is an enediol. No 3-keto or CO₂ is in 2JKV.Source: compiled oxidative decarboxylation · Rhea 10116
⑥ — Glu191B ★ tautomerizes the enediol → Ru5P (hypothetical, lit.-based) Gold H⁺ rides from Glu191B OE1 onto enediol C2; the enediol fades to schematic Ru5P. Glu191B OE1 ⋯ NAP C4N = 7.66 Å on this binary. Net: 6PG + NADP⁺ → Ru5P + CO₂ + NADPH + H⁺ — one H⁺, the same count as G6PD.Source: UniProt P52209 ACT_SITE Glu191 donor · 2JKV OE1⋯C4N
⑦ — Ru5P + NADPH leave — RPI / RPE next [schematic] Ru5P and NADPH depart in opposite directions. Ru5P feeds RPI (R5P) and RPE (Xu5P). NADPH is the second oxidative-PPP payoff.Source: PPP bookkeeping

How to read this page — a first-pass primer First pass: Setup (empty pocket, Lys184B ★ / Glu191B ★ on the dimer interface) → ① NADP⁺ docks → ② 6PG schematic docks → ③ gold H⁺ O3 → NZ (parks) → ④ blue hydride C3 → C4N, 6PG becomes 3-keto, NADP⁺ becomes NADPH → ⑤ CO₂ leaves, enediol remains → ⑥ Glu191B tautomer → Ru5P → ⑦ Ru5P and NADPH leave opposite ways. Second pass: 4.84 Å and 7.66 Å are crystal facts on 2JKV; 6PG and the H spheres are [schematic]. Third pass: open “Disagreements” for dimer-interface residues, no ternary, and concerted vs split.
Chemistry primer — NADP⁺-dependent oxidative decarboxylation 6PG is a C6 sugar acid phosphate. Removing the C3-OH proton and the C3 hydride leaves a ketone at C3. That 3-keto loses C1 as CO₂; the remaining five-carbon enediol tautomerizes to ribulose 5-phosphate. NADP⁺ accepts the hydride at nicotinamide C4. Gold = H⁺. Blue = hydride H⁻. Both G6PD and PGD release one H⁺: net 6PG + NADP⁺ → Ru5P + CO₂ + NADPH + H⁺ (Rhea 10116).
Words used on screen — dimer interface · 3-keto · Ru5P Dimer interface — Lys184B / Glu191B belong to chain B against NAP on chain A. 3-keto-6PG — the hydride product, not deposited. Ru5P — D-ribulose 5-phosphate, the PGD product. NAP — PDB ligand code for NADP/NADPH on 2JKV.

Legend & Fidelity

Mechanism fidelity — measured vs. inferred The measured layer: 2JKV (2.53 Å) with NADPH; Lys184B NZ ⋯ NAP C4N = 4.84 Å; Glu191B OE1 ⋯ C4N = 7.66 Å. The inferred layer ([schematic]): 6PG body, 3-keto, enediol, Ru5P, CO₂, transferring H⁺/H⁻ spheres, NADP⁺→NADPH label switch, and product leave. Binding order is compiled staging, not a kinetic fit. The protein mesh is static. Schematic contacts are not geomClaims.
Disagreements on record (a) Dimer interface. Lys184B / Glu191B, not same-chain Lys184A (~42 Å). Mixing them is the classic 6PGDH error on this mesh. (b) No ternary. 2JKV has NADPH, not 6PG; the sugar is [schematic]. (c) Concerted vs split. Compiled 6PGDH writes oxidation + decarboxylation + tautomer as one cycle; this page splits them (③–⑥) for 1-event/1-step teaching. (d) NADPH vs NADP⁺. The crystal ligand is NADPH; the binding story stages NADP⁺ then relabels NADPH after the hydride. (e) H⁺ bookkeeping. The net is 6PG + NADP⁺ → Ru5P + CO₂ + NADPH + H⁺ — one H⁺, the same count as G6PD; the cartoon parks that H⁺ on Lys184B (protonation-state inversion, lit.). (f) 4GWG apo is not this mesh.
Regulation — NADPH product · oxidative PPP gate NADPH is both the product here and the second reductive payoff of oxidative PPP — named, not drawn as a PGD·NADPH product crystal beyond 2JKV. Oxidative PPP flux is often discussed with G6PD as the committed step; this page is the CO₂-releasing third enzyme.Source: textbook oxidative PPP
Kinetics scope (no measured timecourse on this page) One 6PG → Ru5P + CO₂ + NADPH event is drawn, not a steady-state run. Compiled BRENDA values for EC 1.1.1.44 are not re-asserted here — no measured k_cat/K_m on this page [schematic]. Pair with a kinetics chapter.Source: BRENDA EC 1.1.1.44 — no k_cat/K_m re-asserted
Sequence Human PGD UniProt P52209 · NCBI Gene 5226. Screen uses 2JKV PDB-author numbering (Lys184B, Glu191B). The mesh is chain A; catalytic residues from chain B use B-suffixed cat keys.
Simulation map — what you see is what is written Setup = 2JKV catalytic pocket empty (opaque, run:null). ① NADP⁺ moves in (crystal A500). ② 6PG moves in (schematic). ③ gold H⁺ + gold arrow O3 → Lys184B NZ (parks). ④ slow-mo: blue hydride H⁻ + blue arrow C3 → C4N; 6PG fades to 3-keto; NADP⁺ relabels NADPH; parked gold H⁺ remains. ⑤ CO₂ born and leaves; 3-keto fades to enediol. ⑥ gold H⁺ Glu191B OE1 → C2; enediol fades to Ru5P. ⑦ Ru5P and NADPH leave opposite ways. Only these events move.
Sources — bibliography of this page S1 — PDB 2JKV: human 6PGDH + NADPH, 2.53 Å — public coordinates; measured NZ⋯C4N = 4.84 Å, OE1⋯C4N = 7.66 Å S2 — Sequence / ACT_SITE: UniProt P52209 (human PGD) · NCBI Gene 5226 · Rhea 10116 · Lys184 acceptor · Glu191 donor S3 — Kinetics: BRENDA EC 1.1.1.44 — 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., 6PG on 2JKV, 3-keto / enediol / Ru5P identity, H⁺/H⁻ flight, CO₂ leave), the pose is drawn schematically and labeled as such in the narration.

NADP-binding domainC-domainONH⁺ (gold)H⁻ hydride (blue)