Fructose-1,6-bisphosphatase - 3D Mechanism Simulator

Loading structural data… (5LDZ)

References & Databases

START HERE — how to read F1,6BP + H₂O → F6P + Pi A metal-OH hydrolysis cartoon on the human liver FBPase frame that actually exists: 5LDZ (2.20 Å) with Zn and a metal-bound water. No FBP is deposited on any human P09467 crystal. The sugar is a pig 1FBP overlay (numbering −1, Cα RMSD 1.07 Å) plus a schematic C1-phosphate. AMP on 1FTA/1FBP is allosteric — not this pocket. Physiological metal is Mg/Mn; this crystal holds Zn. Asp119 ★ is in the metal shell, not a covalent nucleophile. A-page (no E~P).
Crystal structures PDB 5LDZ — human liver FBPase, 2.20 Å, Zn + sulfate (Ruf 2016). Coordinates are public. Chain F keeps Gly27. PDB 1FBP supplies the pig F6P overlay only. 1FTA is the AMP allosteric crystal — wrong pocket, not used as the catalytic ligand.
Mechanism — metal-OH attack at C1-P UniProt P09467 EC 3.1.3.11: F1,6BP + H₂O → F6P + Pi. Ke et al., PNAS 1990, PMID:2164670 — pig F6P+AMP+Mg. Ruf et al., Acta Cryst. D 2016, PMID:27841754 — 5LDZ. The catalytic cartoon is metal-activated water at C1-P. Overlay contacts are not geomClaims. Source: UniProt P09467 · Ruf 2016
0 — Setup: Zn present, pocket shown empty 5LDZ holds Zn and HOH502. The pocket is shown empty so ordered binding can start. Zn stays as a named occupant (physiological metal is Mg/Mn). Opaque, run:null (no autoplay). AMP is allosteric.Source: PDB 5LDZ
① — F1,6BP binds (schematic overlay) [schematic] Furanose + C6-P from 1FBP pig overlay (numbering −1). C1-P is not in 1FBP (that crystal holds F6P). Human P09467 has no FBP ternary. Overlay contacts are not geomClaims.Source: overlay 1FBP, not a human ternary
② — Catalytic water binds the metal Water slides into the deposited HOH502 seat (O⋯Zn = 2.08 Å). Asp119 OD2 ⋯ Zn = 1.87 Å. AMP is not this water.Source: 5LDZ HOH502 / Zn F401
③ — Metal-OH forms (hypothetical, lit.-based) A gold H⁺ leaves water H2 toward solvent. Remaining O–H1 = OH⁻. Asp119 ★ is pinned as metal-shell context, not a covalent nucleophile. Compiled FBPase writes this with the attack; this page splits them.Source: compiled metal-OH hydrolase · 5LDZ occupancy
④ — OH⁻ attacks C1-P → F6P + Pi (hypothetical, lit.-based) The OH⁻ (blue arrow = nucleophile, not a hydride) attacks the C1-phosphate. F1,6BP fades to F6P (1FBP overlay; bridge O1 stays as C1–OH) and schematic Pi (fourth O = attacking OH⁻). Slow-motion on purpose.Source: EC 3.1.3.11 C1-P hydrolysis
⑤ — F6P leaves — G6Pase is next F6P and schematic Pi depart in opposite directions. Zn stays. F6P feeds PGI toward G6Pase. AMP allostery is not this motion.Source: GNG bookkeeping

How to read this page — a first-pass primer First pass: Setup (Zn present, pocket empty) → ① schematic FBP docks → ② water docks at HOH502 → ③ gold H⁺ leaves water (metal-OH) → ④ blue OH⁻ attacks C1-P, FBP becomes F6P + Pi → ⑤ F6P and Pi leave. Second pass: 1.87 Å is a crystal fact on 5LDZ; sugar and C1-P are [schematic]. Third pass: open “Disagreements” for pig overlay, Zn vs Mg, and AMP allostery.
Chemistry primer — C1-P hydrolysis FBPase hydrolyses the C1-phosphate of fructose-1,6-bisphosphate, leaving fructose-6-phosphate. Gold = H⁺. Blue on this page = OH⁻ nucleophile, not hydride. Net: F1,6BP + H₂O → F6P + Pi. AMP binds a different (allosteric) pocket.
Words used on screen — overlay F6P · Zn · AMP allosteric Overlay F6P — 1FBP pig F6P Kabsch-fit onto 5LDZ-F with numbering −1, not a human ternary. Zn — crystal occupant; physiological metal is Mg/Mn. AMP allosteric — 1FTA/1FBP AMP is not the catalytic pocket.

Legend & Fidelity

Mechanism fidelity — measured vs. inferred The measured layer: 5LDZ (2.20 Å) with Zn F401 and HOH502; Asp119 OD2 ⋯ Zn = 1.87 Å; Glu98 / Asp122 / Glu281 metal shell. The inferred layer ([schematic]): FBP (pig overlay + C1-P), transferring H⁺/OH⁻, F6P identity, Pi, 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) No human FBP ternary. P09467 crystals are AMP / allosteric / inhibitor series. (b) Pig overlay ≠ human product co-crystal. 1FBP onto 5LDZ (RMSD 1.07 Å, numbering −1). (c) Zn ≠ physiological metal. UniProt lists Mg/Mn; 5LDZ holds Zn. (d) AMP is allosteric. 1FTA is not this pocket. (e) Concerted vs split. Compiled hydrolase writes water activation + attack as one event; this page splits them (③ then ④). (f) C1-P is schematic. 1FBP holds F6P, not FBP.
Regulation — AMP allosteric · liver vs muscle AMP inhibits at a site away from the catalytic metal (1FTA). That pocket is named, not drawn as C1-P chemistry. Liver FBP1 (this page) vs muscle FBP2 are different genes — FBP2 is not this mesh.Source: UniProt P09467 · Gidh-Jain 1FTA
Kinetics scope (no measured timecourse on this page) One F1,6BP → F6P event is drawn, not a steady-state run. Compiled BRENDA values for EC 3.1.3.11 are not re-asserted here — no measured k_cat/K_m on this page [schematic]. Pair with a kinetics chapter.Source: BRENDA EC 3.1.3.11 — no k_cat/K_m re-asserted
Sequence Human FBP1 UniProt P09467 · NCBI Gene 2203. Screen uses 5LDZ / UniProt numbering (Asp119, Glu98, Glu281). Cα 6–337; gaps 23–26 · 58–71 disordered. Overlay numbering is pig −1.
Simulation map — what you see is what is written Setup = 5LDZ pocket empty, Zn visible (opaque, run:null). ① schematic FBP moves in. ② water moves in at HOH502. ③ gold H⁺ leaves water H2 (metal-OH). ④ slow-mo: blue OH⁻ attacks C1-P; FBP fades to F6P + Pi; water consumed. ⑤ F6P and Pi leave opposite ways; Zn stays. Only these events move.
Sources — bibliography of this page S1 — PDB 5LDZ: human liver FBPase, 2.20 Å, Zn + HOH — public coordinates; measured OD2⋯Zn = 1.87 Å S2 — PDB 1FBP: pig F6P overlay onto 5LDZ (Cα RMSD 1.07 Å, numbering −1) — [schematic] sugar, not a human ternary S3 — Ruf et al., Acta Cryst. D 2016, PMID:27841754 — 5LDZ S4 — Sequence: UniProt P09467 (human FBP1) · NCBI Gene 2203 S5 — Kinetics: BRENDA EC 3.1.3.11 — 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., FBP identity, C1-P, OH⁻ flight, product release), the pose is drawn schematically and labeled as such in the narration.

N-domainC-domainONH⁺ (gold)OH⁻ (blue)