Medium-chain acyl-CoA dehydrogenase - 3D Mechanism Simulator

Loading structural data… (8SGP)

References & Databases

START HERE — how to read octanoyl-CoA + ETF_ox + H⁺ → (2E)-octenoyl-CoA + ETF_red An acyl-CoA dehydrogenase cartoon on the human MCAD frame that actually exists: 8SGP (2.69 Å EM) chain A with crystal FAD. Occupancy is FAD, not octanoyl-CoA — never read the flavin as substrate. Octanoyl-CoA is a pig 3MDE overlay [schematic], not a deposited ternary. Overlay Å are not geomClaims. Glu401 ★ on this mesh is UniProt numbering (mature protein is Glu376, the Cα pro-R proton base). Transit 1–25 is not this mesh (Cα 36–420). Gold is H⁺ from C2. Blue is hydride C3 → FAD N5 (flavin N5 acceptor; C4a/C4X is the adjacent atom, adenine C4A is a different atom). FAD stays prosthetic. ETF reoxidation is named, not animated. 1T9G ETF complex is a drawer companion. ACADL/S/VL are other genes. Measured Å are deposited 8SGP pairs only.
Crystal / EM structures PDB 8SGP — human liver WT MCAD + FAD, 2.69 Å EM (Zhang 2023). Coordinates are public. Occupancy is FAD. PDB 3MDE — pig MCAD + octanoyl-CoA, overlay source only (Kim 1993). 1T9G is an MCAD·ETF complex — named companion, not this motion. Human ACADM UniProt P11310.
Mechanism — Glu401 abstracts C2; hydride to FAD N5 UniProt P11310 EC 1.3.8.7: a medium-chain acyl-CoA is dehydrogenated to the trans-2-enoyl-CoA; electrons leave via ETF. On this mesh the catalytic glutamate is Glu401 (mature protein is Glu376, the Cα pro-R proton base). Isoalloxazine C4a is atom C4X on 8SGP. ACADL/S/VL are other genes. Source: UniProt P11310 · Zhang 2023 · Kim 1993
0 — Setup: FAD prosthetic, empty of substrate 8SGP occupancy is FAD. The acyl pocket is shown empty so binding can start. Opaque, run:null (no autoplay). Glu401 ★ is the catalytic base on this UniProt-numbered mesh. Transit 1–25 is not this mesh. 1T9G ETF is not this motion.Source: PDB 8SGP (2.69 Å EM)
① — Octanoyl-CoA binds [schematic] Octanoyl-CoA docks from a pig 3MDE overlay onto this 8SGP FAD mesh — not a deposited ternary. FAD is still the prosthetic, not the substrate. Thr193 OG1 ⋯ FAD N5 = 2.90 Å is deposited 8SGP. Overlay C2/C3 distances are not geomClaims. Teaching chain is C8.Source: 8SGP Thr193/FAD; overlay 3MDE
② — Glu401 takes the C2 proton (hypothetical, lit.-based) Gold H⁺ rides from octanoyl C2 to Glu401 OE2. On this mesh the atom is UniProt Glu401 (mature protein is Glu376, the Cα pro-R proton base). Glu401 OE2 ⋯ FAD N5 = 7.30 Å is deposited 8SGP empty of substrate — not a catalytic contact claim. Overlay C2 distances are not geomClaims. Gold = H⁺.Source: compiled ACAD Glu · UniProt P11310 · 8SGP Glu401/FAD
③ — Hydride C3 → FAD N5 → enoyl + FADH₂ (hypothetical, lit.-based) Blue hydride rides from octanoyl C3 onto FAD N5 (flavin N5 hydride acceptor; C4a/C4X is the adjacent atom, adenine C4A is a different atom). Octanoyl-CoA cross-fades in place to schematic (2E)-octenoyl-CoA. FAD stays and relabels FADH₂ — prosthetic, not substrate. Slow-motion on purpose. FAD N5 ⋯ C4X = 1.30 Å is deposited 8SGP. Overlay C3 distances are not geomClaims.Source: compiled acyl-CoA dehydrogenase · 8SGP FAD
④ — ETF reoxidation — named, not animated (hypothetical, lit.-based) Electron-transfer flavoprotein (ETF) reoxidizes FADH₂ → FAD. That complex is named, not animated — 1T9G is a drawer companion, not this mesh. No ETF cartoon flies. FAD stays prosthetic. The parked gold H⁺ is consumed in the net equation.Source: compiled ETF reoxidation · PDB 1T9G named only
⑤ — Enoyl-CoA leaves — ECHS1 next [schematic] (2E)-Octenoyl-CoA departs. FAD stays — prosthetic, not substrate. Teaching product is C8 enoyl. ECHS1 (next) is taught on crotonyl-CoA (C4) — a chain-length jump, not the same molecule. This page does not hydrate and does not run ACADL/S/VL. Overlay Å are not geomClaims.Source: β-oxidation bookkeeping · EC 1.3.8.7

How to read this page — a first-pass primer First pass: Setup (FAD prosthetic, empty of substrate, Glu401 ★) → ① schematic octanoyl-CoA docks → ② gold H⁺ C2 → Glu401 → ③ blue hydride C3 → FAD N5, fade to enoyl, FADH₂ → ④ ETF reoxidation named, not animated → ⑤ enoyl leaves; FAD stays; ECHS1 next (C8 → C4 teaching jump). Second pass: 2.90 / 7.30 / 2.87 / 2.46 / 2.57 / 1.30 Å are crystal facts on 8SGP empty of substrate; octanoyl-CoA / enoyl are [schematic]; FAD is never substrate. Teaching product is C8; ECHS1 is taught on C4. Third pass: open “Disagreements” for occupancy vs substrate, UniProt Glu401 vs mature Glu376, pig overlay vs this mesh, and ACADL/S/VL vs this gene.
Chemistry primer — FAD-dependent α,β-dehydrogenation MCAD abstracts the acyl C2 proton (Glu401) and sends the C3 hydride to the flavin. Teaching product is C8 trans-2-enoyl-CoA. ECHS1 (next) hydrates a C4 crotonyl-CoA — a chain-length jump, not the same molecule. Electrons leave the prosthetic FAD via ETF — not drawn as a flying protein. Gold is H⁺. Blue is hydride, not oxygen nucleophile. This is not ACADL, ACADS, or ACADVL.
Words used on screen — prosthetic · overlay · Glu401 ★ · C4X Prosthetic — FAD is bound on 8SGP and stays; it is not the fatty acyl substrate. Overlay — octanoyl-CoA pose is pig 3MDE Kabsch-fitted onto this mesh, not deposited. Glu401 ★ — PDB / UniProt id on this frame; mature literature often says Glu376. C4X — isoalloxazine C4a on this mesh; adenine C4A is a different atom.

Legend & Fidelity

Mechanism fidelity — measured vs. inferred The measured layer: 8SGP (2.69 Å EM) human MCAD + FAD; Thr193 OG1 ⋯ N5 = 2.90 Å; Glu401 OE2 ⋯ N5 = 7.30 Å (empty of substrate); Thr161 OG1 ⋯ N1 = 2.87 Å; Thr403 OG1 ⋯ O2B = 2.46 Å; Gln405 NE2 ⋯ O2B = 2.57 Å; FAD N5 ⋯ C4X = 1.30 Å. The inferred layer ([schematic]): octanoyl-CoA overlay, (2E)-octenoyl-CoA, transferring H⁺ / hydride spheres, ETF name, product leave. Binding order is compiled staging, not a kinetic fit. The protein mesh is static. Overlay Å are not geomClaims. FAD is prosthetic, not substrate.
Disagreements on record (a) Occupancy vs substrate. 8SGP holds FAD, not octanoyl-CoA. (b) Numbering. Screen ★ is Glu401 (UniProt / this PDB). Mature pig/human literature often calls the same glutamate Glu376 (offset about +25). (c) 3MDE vs 8SGP. Pig overlay, not this ternary. Overlay C2/C3 distances are not geomClaims. (d) Transit 1–25 is not this mesh (Cα 36–420). (e) 1T9G ETF complex is named, not this motion. (f) Concerted vs split proton/hydride — this page splits ② then ③ for 1-event/1-step teaching. (g) ACADL / ACADS / ACADVL are other genes. (h) Tetramer assembly is not this cartoon.
Regulation — isoforms · MCAD deficiency This spiral is ACADM / MCAD only. Very-long-, long-, and short-chain acyl-CoA dehydrogenases (ACADVL / ACADL / ACADS) are other genes — not this mesh. Human MCAD deficiency alleles are named, not simulated. ETF is the physiological electron acceptor; reoxidation is named, not animated. Matrix localization is assumed, not a catalytic event on this page.Source: UniProt P11310 · PDB 8SGP · Zhang 2023
Kinetics scope (no measured timecourse on this page) One octanoyl-CoA + ETF_ox + H⁺ → (2E)-octenoyl-CoA + ETF_red event is drawn, not a steady-state run. Compiled BRENDA values for EC 1.3.8.7 are not re-asserted here — no measured k_cat/K_m on this page [schematic]. Pair with a kinetics chapter.Source: BRENDA EC 1.3.8.7 — no k_cat/K_m re-asserted
Sequence Human ACADM UniProt P11310 · NCBI Gene 34. This screen uses 8SGP numbering (Glu401). Chain A. Cα 36–420. Transit 1–25 not this mesh.
Simulation map — what you see is what is written Setup = 8SGP FAD seated, acyl pocket empty (opaque, no autoplay). ① schematic octanoyl-CoA moves in. ② gold H⁺ C2 → Glu401. ③ slow-mo: blue hydride C3 → FAD N5; octanoyl-CoA fades to enoyl; FAD relabels FADH₂. ④ ETF reoxidation named; FAD relabels FAD. ⑤ enoyl leaves; FAD stays. Only these events move.
Sources — bibliography of this page S1 — PDB 8SGP: human MCAD + FAD, 2.69 Å EM — public coordinates; measured Thr193 OG1⋯N5 = 2.90 Å · Glu401 OE2⋯N5 = 7.30 Å · Thr161 OG1⋯N1 = 2.87 Å · Thr403 OG1⋯O2B = 2.46 Å · Gln405 NE2⋯O2B = 2.57 Å · N5⋯C4X = 1.30 Å S2 — Zhang et al., 2023, PMID:37839702 — human liver WT MCAD EM + FAD S3 — Kim et al., Proc Natl Acad Sci USA 1993, PMID:8356049 — pig MCAD + octanoyl-CoA (3MDE overlay only) S4 — Sequence: UniProt P11310 · NCBI Gene 34 · ETF companion 1T9G named only S5 — Kinetics: BRENDA EC 1.3.8.7 — no k_cat/K_m re-asserted on this page

› Backbones and FAD poses are taken directly from the listed PDB entries, superposed into one common frame. Where no crystalline state exists for a step (e.g., octanoyl-CoA on 8SGP, enoyl-CoA, proton/hydride flight, ETF, product release), the pose is drawn schematically and labeled as such in the narration. Occupancy is FAD, not octanoyl-CoA. Overlay Å are not geomClaims.

N-domainC-domainONH⁺ (gold)hydride (blue)