Acetyl-CoA carboxylase 1 - 3D Mechanism Simulator

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References & Databases

START HERE — how to read HCO₃⁻ + acetyl-CoA + ATP → malonyl-CoA + ADP + Pi + H⁺ A biotin-carboxylase cartoon on the human ACC1 frame that actually exists: 8XKZ (2.55 Å EM) chain C, citrate-filament core with crystal BTN covalently on Lys786. Occupancy is BTN only, not ATP, not acetyl-CoA, not malonyl, not citrate — never copy the PDB title “ACC1-CITRATE” as occupancy. There is no citrate ligand and no MG entity. Citrate induced the filament and is Regulation, not a pocket ligand. Lys786 ★ is the biotinylation site (NZ⋯C11 = 1.36 Å LINK) — prosthetic N6-biotinyllysine carrier, not the BC carboxylation center. UniProt ACT_SITE Arg441 is BC, ~69 Å from BTN — named, not starred, not a geomClaim. BTN is CT-docked (Asp2000 OD2⋯N1 = 3.01 Å). ATP / HCO₃⁻ / acetyl-CoA / malonyl / carboxybiotin / ADP / Pi are [schematic]. White is carboxyl in flight, not hydride. BTN stays prosthetic. ACC2 is another gene. FASN next. Measured Å are deposited 8XKZ BTN pairs only.
Crystal / EM structures PDB 8XKZ — human ACC1 citrate-filament core + BTN, 2.55 Å cryo-EM, EMD-38432 (Zhou 2024). Coordinates are public. Occupancy is BTN only. Human ACC1 UniProt Q13085.
Mechanism — Lys786-biotin; BC then CT UniProt Q13085 EC 6.4.1.2: HCO₃⁻ + acetyl-CoA + ATP → malonyl-CoA + ADP + Pi + H⁺. Two half-reactions: (1) biotin-N1 carboxylation (BC) → carboxybiotin + ADP + Pi. (2) carboxyl transfer onto acetyl-CoA C2 (CT) → malonyl-CoA. Zhou et al., Sci. Adv. 2024, PMID:39383219. ACC2 / ACACB is another gene. Source: UniProt Q13085 · Zhou 2024
0 — Setup: empty carboxylase pocket 8XKZ occupancy is BTN only (covalent biotin on Lys786), not ATP, not acetyl-CoA, not malonyl, not citrate. The PDB title says citrate-induced filament (ACC1-CITRATE) — that is not occupancy (no citrate ligand, no MG entity). Prosthetic BTN stays. Opaque, run:null (no autoplay). Lys786 ★ is the biotinylation site (prosthetic carrier, not the BC center). Arg441 is BC ACT_SITE, ~69 Å from BTN — named, not starred. ACC2 is another gene. Cα 98–2337 with gaps 1190–1230 / 1256–1283 / 1333–1351 / 1519–1524.Source: PDB 8XKZ (2.55 Å EM)
① — Bicarbonate binds [schematic] HCO₃⁻ docks near biotin N1 — not deposited. 8XKZ holds prosthetic biotin, not bicarbonate. Citrate induced this filament and is not a pocket ligand.Source: compiled BC staging on 8XKZ BTN pose
② — ATP binds Schematic ATP docks on the CT-docked biotin pose — [schematic], never a crystal nucleotide. Lys786 NZ ⋯ BTN C11 = 1.36 Å is the deposited covalent LINK, not an ATP geomClaim. Arg441 is ~69 Å away in BC — not a geomClaim. No crystal Mg.Source: 8XKZ BTN pose rebuilt as ATP seat
③ — Biotin-N1 is carboxylated → carboxybiotin + ADP + Pi (hypothetical, lit.-based) Schematic bicarbonate carbon (white ball + white arrow) carboxylates biotin N1. BTN + ATP fade in place to schematic carboxybiotin and schematic ADP; Pi leaves. Never label BTN as substrate. BC carboxylation is compiled on this CT-docked pose — Arg441 is 69 Å away. Slow-motion on purpose. White = carboxyl, not hydride.Source: compiled ACC1 BC half · Zhou 2024
④ — Acetyl-CoA binds Schematic acetyl-CoA docks on the CT-docked biotin pose — [schematic], not deposited. Asp2000 OD2 ⋯ BTN N1 = 3.01 Å is deposited (carboxybiotin keeps that N1 pose). Val1857 CG1 ⋯ BTN O11 = 3.08 Å is deposited. Pi already left. ADP stays until leave. Never label BTN as acetyl-CoA.Source: PDB 8XKZ BTN CT contacts
⑤ — Carboxyl transfer → malonyl-CoA (hypothetical, lit.-based) Carboxybiotin CX (white ball + white arrow) transfers onto acetyl C2. Carboxybiotin + acetyl-CoA cross-fade in place to crystal BTN and schematic malonyl-CoA. Val1857 CG1 ⋯ BTN O11 = 3.08 Å is deposited. Slow-motion on purpose. White = carboxyl, not hydride. BTN is prosthetic, not substrate.Source: compiled ACC1 CT half · Zhou 2024
⑥ — Malonyl-CoA and ADP leave — FASN next Malonyl-CoA and schematic ADP depart in opposite directions. Prosthetic biotin stays. Pi already left. Malonyl-CoA is the substrate of FASN (next). This page does not make palmitate. 8XKZ occupancy is BTN, not acetyl-CoA. Title ACC1-CITRATE is the filament, not a citrate ligand. ACC2 is another gene. Net EC H⁺ is not a gold sphere.Source: FAS bookkeeping · EC 6.4.1.2

How to read this page — a first-pass primer First pass: Setup (empty pocket, Lys786 ★, BTN stays, occupancy is BTN only) → ① schematic HCO₃⁻ docks → ② schematic ATP docks → ③ white carboxyl onto N1, fade to carboxybiotin + ADP, Pi leaves → ④ schematic acetyl-CoA docks → ⑤ white carboxyl onto acetyl C2, fade to malonyl-CoA + crystal BTN → ⑥ malonyl-CoA and ADP leave opposite; BTN stays; FASN next. Second pass: 1.36 / 3.01 / 3.08 Å are crystal facts on 8XKZ BTN occupancy; ATP, HCO₃⁻, acetyl-CoA, malonyl, carboxybiotin, ADP, Pi are [schematic]. The 69 Å Arg441 gap is not a geomClaim. Third pass: open “Disagreements” for title vs occupancy, BTN vs substrate, Arg441 vs Lys786 ★, citrate filament vs ligand, and ACC2.
Chemistry primer — BC carboxylation then CT transfer ACC1 carboxylates acetyl-CoA for cytosolic malonyl-CoA. Bicarbonate carbon is activated by ATP; biotin-N1 is carboxylated and ADP + Pi form. Carboxybiotin then transfers that carboxyl onto acetyl-CoA C2; malonyl-CoA leaves and biotin stays prosthetic. White = carboxyl in flight (onto N1, then onto acetyl C2). This is not ACLY (citrate cleavage) and not ACC2.
Words used on screen — BTN prosthetic · Lys786 ★ · filament ≠ ligand · ACC2 other gene BTN prosthetic — covalent biotin on Lys786, not a substrate and not acetyl-CoA. Lys786 ★ — biotinylation site (this PDB = UniProt): prosthetic N6-biotinyllysine (MOD_RES 786), the biotin carrier — not the BC carboxylation center. Filament ≠ ligand — title ACC1-CITRATE is citrate-induced filament biology, not a citrate ligand. ACC2 other gene — ACACB / mito CPT1 gate, not this mesh. Arg441 — BC ACT_SITE, ~69 Å from BTN, named not starred.

Legend & Fidelity

Mechanism fidelity — measured vs. inferred The measured layer: 8XKZ (2.55 Å EM) human ACC1 citrate-filament core + BTN; Lys786 NZ ⋯ BTN C11 = 1.36 Å; Asp2000 OD2 ⋯ BTN N1 = 3.01 Å; Val1857 CG1 ⋯ BTN O11 = 3.08 Å. The inferred layer ([schematic]): ATP, HCO₃⁻, carboxybiotin, acetyl-CoA, malonyl-CoA, ADP, Pi, transferring carboxyl spheres, product leave. Binding order is compiled staging, not a kinetic fit. The protein mesh is static. Schematic Å are not geomClaims. The ~69 Å Arg441 gap is not a geomClaim. Title “ACC1-CITRATE” is not occupancy.
Disagreements on record (a) Occupancy vs title. 8XKZ holds BTN only, not ATP, not acetyl-CoA, not malonyl, not citrate. The title names a citrate-induced filament — no citrate ligand, no MG entity. (b) BTN vs substrate. BTN is prosthetic biotin, not acetyl-CoA. (c) Lys786 ★ vs Arg441. Screen star is the biotinylation lysine. Arg441 is BC ACT_SITE, ~69 Å from BTN — named, not starred. (d) Carboxybiotin is compiled identity, not this occupancy. (e) Concerted vs split BC/CT — this page splits ③ then ⑤ for 1-event/1-step teaching. (f) BC carboxylation is compiled on a CT-docked BTN pose. (g) ACC2 / ACACB is another gene. (h) Phosphorylated inactive filaments = Regulation, not this cartoon. (i) Cα gaps 1190–1230 / 1256–1283 / 1333–1351 / 1519–1524. (j) Chains C and D; teaching = chain C. (k) Net EC H⁺ is not a gold sphere.
Regulation — citrate filament · phosphorylation · ACC2 This carboxylation is cytosolic ACC1 / ACACA only. ACC2 / ACACB is another gene — not this mesh. Citrate induced the 8XKZ filament and is named here, not drawn as a pocket ligand. Phosphorylated inactive filaments are named, not animated. Filament vs dimer is drawer-only.Source: UniProt Q13085 · PDB 8XKZ · Zhou 2024
Kinetics scope (no measured timecourse on this page) One HCO₃⁻ + acetyl-CoA + ATP → malonyl-CoA + ADP + Pi + H⁺ event is drawn, not a steady-state run. Compiled BRENDA values for EC 6.4.1.2 are not re-asserted here — no measured k_cat/K_m on this page [schematic]. Pair with a kinetics chapter.Source: BRENDA EC 6.4.1.2 — no k_cat/K_m re-asserted
Sequence Human ACC1 UniProt Q13085 · NCBI Gene 31. This screen uses 8XKZ numbering (Lys786 = UniProt Lys786; Arg441 named). Chain C. Cα 98–2337 with gaps 1190–1230 / 1256–1283 / 1333–1351 / 1519–1524.
Simulation map — what you see is what is written Setup = 8XKZ pocket empty, BTN stays (opaque, no autoplay). ① schematic HCO₃⁻ moves in. ② schematic ATP moves in. ③ slow-mo: white carboxyl onto N1; fade to carboxybiotin + ADP; Pi leaves. ④ schematic acetyl-CoA moves in. ⑤ slow-mo: white carboxyl onto acetyl C2; fade to malonyl-CoA + crystal BTN. ⑥ malonyl-CoA and ADP leave opposite; BTN stays. Only these events move.
Sources — bibliography of this page S1 — PDB 8XKZ: human ACC1 citrate-filament core + BTN, 2.55 Å EM — public coordinates; measured Lys786 NZ⋯BTN C11 = 1.36 Å · Asp2000 OD2⋯BTN N1 = 3.01 Å · Val1857 CG1⋯BTN O11 = 3.08 Å S2 — Zhou et al., Sci. Adv. 2024, PMID:39383219 — human ACC1 citrate filament; biotin CT-docked S3 — Sequence: UniProt Q13085 · NCBI Gene 31 S4 — Kinetics: BRENDA EC 6.4.1.2 — no k_cat/K_m re-asserted on this page

› Backbones and the BTN pose are taken directly from the listed PDB entries, superposed into one common frame. Where no crystalline state exists for a step (e.g., ATP, HCO₃⁻, carboxybiotin, acetyl-CoA, malonyl-CoA, ADP, Pi, carboxyl flight, product leave), the pose is drawn schematically and labeled as such in the narration. Occupancy is BTN only, not ATP/acetyl-CoA/malonyl/citrate. Schematic Å are not geomClaims. Title ACC1-CITRATE is the filament, not occupancy.

BCBCCPCTONcarboxyl (white)