6-Phosphogluconolactonase - 3D Mechanism Simulator

Loading structural data… (1PBT)

References & Databases

START HERE — how to read 6PGL + H₂O → 6PG + H⁺ A single lactone-hydrolysis cartoon on a bacterial PGLS pocket. Real crystal: 1PBT (1.70 Å), T. maritima TM1154. Human PGLS (O95336) has no PDB — this mesh is a species hedge. 1PBT is apo: deposited SO₄ / Tris / ethylene glycol / formate are crystallization buffer, not the lactone. Every substrate/water/product pose is [schematic]. His138 ★ sits in the GPDGH motif (134–138) and is shown activating water (gold H⁺ parks on NE2). The leftover OH⁻ (blue arrow = nucleophile, not hydride) attacks lactone C1 and the ring opens to 6-phosphogluconate. No Å is claimed for substrate contacts. H6PD / 8EM2 is a different gene.
Crystal structure PDB 1PBT — TM1154, 6-phosphogluconolactonase from Thermotoga maritima, 1.70 Å, Midwest Center for Structural Genomics (deposited 2003; journal “to be published”). Coordinates are public. Chain A, GPDGH motif 134–138. HET = MSE (1/25/133), SO4 302/303, TRS 301, EDO 304, FMT 305, HOH. SO4-302 sits near His138 (buffer occupancy, not a geomClaim). Human PGLS UniProt O95336 has no PDB. H6PD 8EM2 is a different gene (ER bifunctional), not this page.
Mechanism — His-activated water, OH⁻ at C1, ring open EC 3.1.1.31 hydrolyses 6-phospho-D-glucono-1,5-lactone to 6-phospho-D-gluconate (Rhea 12556). This page is a hydration cartoon: His138 ★ abstracts a water proton; OH⁻ attacks carbonyl C1; the δ-lactone opens to the linear (open-chain) 6PG carboxylate; net H⁺ leaves. Compiled lactonase writes water activation with the attack; this page splits them. Arg167 / Arg70 / Asp136 are named as pocket context, not stars. Source: UniProt O95336 · Tm Q9X0N8 · Rhea 12556 · PDB 1PBT
0 — Setup: apo GPDGH pocket The catalytic GPDGH motif presents His138 ★. 1PBT is apo — SO4/TRS/EDO/FMT are buffer, not substrate — so the pocket is shown empty for the catalytic story. Opaque, run:null (no autoplay). Human O95336 has no PDB; this mesh is T. maritima. Arg167 / Arg70 / Asp136 are context.Source: PDB 1PBT (1.70 Å)
① — 6-Phosphoglucono-δ-lactone binds [schematic] The G6PD product docks with carbonyl C1 toward His138 ★. 1PBT has no lactone ligand; SO4 near His138 is buffer occupancy, not a geomClaim. The substrate is the δ-lactone, not 6-phosphogluconate (that is the product).Source: schematic pose (no lactone in 1PBT)
② — Catalytic water binds the attacking face [schematic] A catalytic water slides in toward lactone C1. This cartoon aims H2 at His138 ★ NE2; O–H1 is the nucleophile in the next overlay. No catalytic-water coordinates are claimed as a unique 1PBT catalytic water. Arg167 is named as a polarizing partner on the carbonyl, not the base.Source: water-activating His, GPDGH motif on 1PBT
③ — His138 ★ abstracts the water H⁺ (hypothetical, lit.-based) A gold H⁺ sphere rides a gold arrow from water H2 to His138 NE2 and parks. Removing H2 leaves O–H1 = OH⁻. Compiled lactonase writes this with the attack; this page splits them. Arg167 is named, not the star.Source: GPDGH His138 on 1PBT · compiled EC 3.1.1.31
④ — OH⁻ attacks C1 → lactone opens to 6PG (hypothetical, lit.-based) The OH⁻ (blue arrow = nucleophile, not a hydride) attacks lactone C1. The ring cross-fades in place to schematic 6-phosphogluconate. Parked gold H⁺ stays on His138. Slow-motion on purpose.Source: Rhea 12556 ring-opening hydrolysis
⑤ — 6PG + H⁺ leave — PGD is next [schematic] 6-Phosphogluconate and the net gold H⁺ depart in opposite directions. Water was consumed. 6PG is the substrate of PGD; NADPH from G6PD is not this enzyme’s product.Source: PPP bookkeeping · EC 3.1.1.31 net H⁺

How to read this page — a first-pass primer First pass: Setup (apo GPDGH, His138 ★, T. maritima mesh) → ① lactone docks → ② water docks → ③ gold H⁺ water H2 → NE2 (parks; water becomes OH⁻) → ④ blue OH⁻ attacks C1, lactone becomes 6PG → ⑤ 6PG and H⁺ leave opposite ways. Second pass: no substrate Å are printed — 1PBT is apo; SO4 is buffer. Third pass: open “Disagreements” for species hedge, buffer occupancy, and concerted vs split.
Chemistry primer — δ-lactone hydrolysis G6PD made a six-membered lactone at C1. Water adds at that carbonyl; the ring opens to a carboxylate (6-phosphogluconate). Gold = H⁺. Blue on this page = OH⁻ nucleophile, not hydride. Net: 6PGL + H₂O → 6PG + H⁺. PGD oxidizes 6PG next.
Words used on screen — GPDGH · apo · species hedge GPDGH — motif 134–138 on 1PBT; His138 ★ is the last residue. Apo — no lactone in the deposit; buffer ligands are named, not drawn as substrate. Species hedge — the mesh is T. maritima TM1154; human O95336 has no PDB. OH⁻ — hydroxide nucleophile after His removes one water proton; blue here is not hydride.

Legend & Fidelity

Mechanism fidelity — measured vs. inferred The measured layer: 1PBT (1.70 Å) T. maritima TM1154 with the GPDGH motif (His138 ★ drawn). Deposited ligands are MSE, SO4, TRS, EDO, FMT, HOH — buffer/solvent, not substrate, not drawn as 6PGL. The inferred layer (all [schematic]): lactone, water, 6PG, transferring H⁺/OH⁻, and product leave. No Å label is drawn for any substrate contact. Binding order is compiled staging, not a kinetic fit. The protein mesh is static.
Disagreements on record (a) Species. Human O95336 has no PDB; 1PBT is T. maritima TM1154 (Q9X0N8). (b) Apo vs occupied. SO4 near His138 is buffer occupancy, not a lactone analog and not a geomClaim. (c) Concerted vs split. Compiled lactonase writes water activation + attack as one event; this page splits them (③ then ④) for 1-event/1-step teaching. (d) Resolution lock. RCSB 1PBT is 1.70 Å, not 1.35 Å. (e) H6PD (O95479 / 8EM2) is a different gene (ER bifunctional), not this page. (f) Arg vs His as base. His138 is the star; Arg167 is named as a polarizing partner, not sold as the general base.
Regulation — oxidative PPP · isoforms PGLS sits between G6PD and PGD on oxidative PPP. Cytosolic PGLS (this page) vs microsomal H6PD are different genes — H6PD is not drawn. No allosteric crystal is claimed here.Source: UniProt O95336 · textbook G6PD → PGLS → PGD
Kinetics scope (no measured timecourse on this page) One 6PGL → 6PG + H⁺ event is drawn, not a steady-state run. Compiled BRENDA values for EC 3.1.1.31 are not re-asserted here — no measured k_cat/K_m on this page [schematic]. Pair with a kinetics chapter.Source: BRENDA EC 3.1.1.31 — no k_cat/K_m re-asserted
Sequence Human PGLS UniProt O95336 · NCBI Gene 25796 (no human PDB). This screen uses T. maritima TM1154 Q9X0N8 numbering (His138 on 1PBT).
Simulation map — what you see is what is written Setup = 1PBT catalytic pocket empty (opaque, run:null). ① lactone moves in (schematic). ② water moves in (schematic). ③ gold H⁺ + gold arrow H2 → His138 NE2 (parks); water becomes OH⁻. ④ slow-mo: blue OH⁻ attacks C1; lactone fades to 6PG; parked gold H⁺ remains; water consumed. ⑤ 6PG and H⁺ leave opposite ways. Only these events move.
Sources — bibliography of this page S1 — PDB 1PBT: TM1154 6-phosphogluconolactonase, T. maritima, 1.70 Å, MCSG — public coordinates; apo (SO4/TRS/EDO/FMT = buffer) S2 — Sequence: UniProt O95336 (human PGLS, no PDB) · UniProt Q9X0N8 (TM_1154) · NCBI Gene 25796 · Rhea 12556 S3 — Kinetics: BRENDA EC 3.1.1.31 — no k_cat/K_m re-asserted on this page

› Backbones are taken directly from the listed PDB entry. 1PBT holds buffer ligands, not a substrate. Where no crystalline state exists for a step (lactone, water, 6PG, H⁺/OH⁻ flight, product release), the pose is drawn schematically and labeled as such in the narration.

N-domainC-domainONH⁺ (gold)OH⁻ (blue)