Short-chain 3-hydroxyacyl-CoA dehydrogenase

Loading structural data… (1F0Y)

References & Databases

START HERE — how to read (3S)-3-hydroxybutanoyl-CoA + NAD⁺ → acetoacetyl-CoA + NADH + H⁺ A 3-hydroxyacyl-CoA dehydrogenase cartoon on the human HADH frame that actually exists: 1F0Y (1.80 Å X-ray) chain A with crystal NAD⁺ and acetoacetyl-CoA. Occupancy is NAD⁺ + the oxo product, not 3-hydroxybutanoyl-CoA — never read CAA as the 3-hydroxy substrate. 3-hydroxy is rebuilt on the CAA pose [schematic]. His158 ★ on this mesh is UniProt His170 (Barycki SITE). Glu170 on this mesh is the catalytic dyad partner of His158 (PDB 1IL0). Transit 1–11 is not this mesh (Cα 12–302). Gold is H⁺ from 3-OH. Blue is hydride C3 → NAD C4N (nicotinamide C4; adenine C4A is a different atom). NAD is a co-substrate and leaves as NADH, not a prosthetic. HADHA/B are other genes. Measured Å are deposited 1F0Y product-complex pairs only.
Crystal / X-ray structures PDB 1F0Y — human heart HADH + NAD⁺ + acetoacetyl-CoA, 1.80 Å X-ray (Barycki 2000). Coordinates are public. Occupancy is NAD⁺ + oxo product. Human HADH UniProt Q16836.
Mechanism — His158 abstracts 3-OH; hydride to NAD C4N UniProt Q16836 EC 1.1.1.35: a (3S)-3-hydroxyacyl-CoA is oxidized to the 3-ketoacyl-CoA; NAD⁺ is the hydride acceptor. On this mesh the catalytic histidine is His158 (UniProt His170). Nicotinamide C4 is atom C4N. HADHA/B are other genes. Source: UniProt Q16836 · Barycki 2000 · Barycki 1999
0 — Setup: empty dehydrogenase pocket 1F0Y occupancy is NAD⁺ + acetoacetyl-CoA (oxo product). The pocket is shown empty so binding can start. Opaque, run:null (no autoplay). His158 ★ is the catalytic base on this mesh (UniProt His170). Transit 1–11 is not this mesh. HADHA/B are other genes.Source: PDB 1F0Y (1.80 Å X-ray)
① — NAD⁺ binds Crystal NAD⁺ docks into the Rossmann pocket — deposited 1F0Y occupancy. NAD is a co-substrate, not a prosthetic (it will leave as NADH). Nicotinamide C4 is atom C4N; adenine C4A is a different atom.Source: PDB 1F0Y NAD
② — 3-Hydroxybutyryl-CoA binds [schematic] (3S)-3-Hydroxybutanoyl-CoA docks on the 1F0Y CAA pose — not a deposited 3-hydroxy. CAA on 1F0Y is acetoacetyl-CoA (oxo product), not the 3-hydroxy substrate. Product-complex Å are not 3-hydroxy geomClaims. Teaching chain is C4.Source: 1F0Y CAA pose rebuilt as 3-hydroxy
③ — His158 takes the 3-OH proton (hypothetical, lit.-based) Gold H⁺ rides from 3-hydroxy O3 to His158 NE2. On this mesh the atom is PDB His158 (UniProt His170). Glu170 on this mesh is the catalytic dyad partner of His158 (PDB 1IL0). Gold = H⁺. Product-complex O3 distances are not 3-hydroxy geomClaims.Source: compiled HADH His · UniProt Q16836 · 1F0Y His158
④ — Hydride C3 → NAD C4N → acetoacetyl-CoA + NADH (hypothetical, lit.-based) Blue hydride rides from 3-hydroxy C3 onto NAD C4N (nicotinamide C4; adenine C4A is a different atom). 3-Hydroxy cross-fades in place to crystal acetoacetyl-CoA. NAD relabels NADH and will leave — co-substrate, not prosthetic. His158 NE2 ⋯ CAA O3 = 2.62 Å is deposited 1F0Y product complex. Slow-motion on purpose. Blue = hydride, not oxygen nucleophile.Source: compiled HADH hydride · 1F0Y NAD/CAA
⑤ — Acetoacetyl-CoA and NADH leave — ACAA2 next Acetoacetyl-CoA and NADH depart in opposite directions. His-H⁺ is released to solvent off-screen (net H⁺ in the equation). NAD is a co-substrate, not a prosthetic. Teaching product is C4 acetoacetyl-CoA. That oxoacyl-CoA is the substrate of ACAA2. This page does not thiolyse and does not run HADHA/B. Product-complex Å are not 3-hydroxy geomClaims.Source: β-oxidation bookkeeping · EC 1.1.1.35

How to read this page — a first-pass primer First pass: Setup (empty pocket, His158 ★) → ① crystal NAD⁺ docks → ② schematic 3-hydroxy docks on CAA pose → ③ gold H⁺ 3-OH → His158 → ④ blue hydride C3 → NAD C4N, fade to acetoacetyl-CoA, NADH → ⑤ oxo and NADH leave opposite; ACAA2 next (C4, same chain). Second pass: 2.62 / 2.48 / 3.46 Å are crystal facts on 1F0Y product complex; 3-hydroxy is [schematic]; CAA is oxo product, not substrate. Teaching product is C4. Third pass: open “Disagreements” for product occupancy vs 3-hydroxy, UniProt His170 vs PDB His158, and HADHA vs this gene.
Chemistry primer — NAD-dependent β-hydroxy oxidation HADH abstracts the 3-hydroxy proton (His158) and sends the C3 hydride to NAD⁺ C4. Teaching product is C4 acetoacetyl-CoA — ACAA2 (next) thiolyses this same chain. NAD is a co-substrate and leaves as NADH. Gold is H⁺. Blue is hydride, not oxygen nucleophile. This is not HADHA/B (trifunctional protein).
Words used on screen — oxo product · schematic 3-hydroxy · His158 ★ · C4N Oxo product — 1F0Y CAA is acetoacetyl-CoA, the dehydrogenase product, not the 3-hydroxy substrate. Schematic 3-hydroxy — teaching substrate rebuilt on that CAA pose. His158 ★ — PDB id on this frame; UniProt His170. C4N — nicotinamide C4 on this mesh; adenine C4A is a different atom.

Legend & Fidelity

Mechanism fidelity — measured vs. inferred The measured layer: 1F0Y (1.80 Å X-ray) human HADH + NAD⁺ + acetoacetyl-CoA; His158 NE2 ⋯ CAA O3 = 2.62 Å; Ser137 OG ⋯ CAA O3 = 2.48 Å; CAA C3 ⋯ NAD C4N = 3.46 Å. The inferred layer ([schematic]): 3-hydroxybutanoyl-CoA rebuilt on the CAA pose, transferring H⁺ / hydride spheres, NAD→NADH relabel, product leave. Binding order is compiled staging, not a kinetic fit. The protein mesh is static. Product-complex Å are not 3-hydroxy geomClaims. CAA is oxo product, not substrate.
Disagreements on record (a) Occupancy vs substrate. 1F0Y holds NAD⁺ + acetoacetyl-CoA (oxo product), not 3-hydroxybutanoyl-CoA. (b) Numbering. Screen ★ is His158 (this PDB). UniProt His170 is the same histidine (mature offset). Glu170 on this mesh is the catalytic dyad partner of His158. (c) Product-complex Å are not 3-hydroxy geomClaims. (d) Transit 1–11 is not this mesh (Cα 12–302). (e) Concerted vs split proton/hydride — this page splits ③ then ④ for 1-event/1-step teaching. (f) HADHA / HADHB (trifunctional protein) are other genes. (g) Dimer assembly is not this cartoon. (h) ACAA2 thiolysis is next, not this page.
Regulation — isoforms · HADH deficiency This spiral is monofunctional HADH only. Mitochondrial trifunctional protein (HADHA / HADHB) is another gene — not this mesh. Human HADH / SCHAD deficiency alleles are named, not simulated. Matrix localization is assumed, not a catalytic event on this page.Source: UniProt Q16836 · PDB 1F0Y · Barycki 2000
Kinetics scope (no measured timecourse on this page) One (3S)-3-hydroxybutanoyl-CoA + NAD⁺ → acetoacetyl-CoA + NADH + H⁺ event is drawn, not a steady-state run. Compiled BRENDA values for EC 1.1.1.35 are not re-asserted here — no measured k_cat/K_m on this page [schematic]. Pair with a kinetics chapter.Source: BRENDA EC 1.1.1.35 — no k_cat/K_m re-asserted
Sequence Human HADH UniProt Q16836 · NCBI Gene 3033. This screen uses 1F0Y numbering (His158 = UniProt His170). Chain A. Cα 12–302. Transit 1–11 not this mesh.
Simulation map — what you see is what is written Setup = 1F0Y pocket empty (opaque, no autoplay). ① crystal NAD⁺ moves in. ② schematic 3-hydroxy moves in on CAA pose. ③ gold H⁺ 3-OH → His158. ④ slow-mo: blue hydride C3 → NAD C4N; 3-hydroxy fades to acetoacetyl-CoA; NAD relabels NADH. ⑤ oxo and NADH leave opposite. Only these events move.
Sources — bibliography of this page S1 — PDB 1F0Y: human HADH + NAD⁺ + acetoacetyl-CoA, 1.80 Å X-ray — public coordinates; measured His158 NE2⋯CAA O3 = 2.62 Å · Ser137 OG⋯CAA O3 = 2.48 Å · CAA C3⋯NAD C4N = 3.46 Å S2 — Barycki et al., 2000, PMID:10840044 — human HADH ternary with NAD⁺ and acetoacetyl-CoA S3 — Barycki et al., 1999, PMID:10231530 — His158 / UniProt His170 as catalytic base S4 — Sequence: UniProt Q16836 · NCBI Gene 3033 S5 — Kinetics: BRENDA EC 1.1.1.35 — no k_cat/K_m re-asserted on this page

› Backbones and NAD / CAA poses are taken directly from the listed PDB entries, superposed into one common frame. Where no crystalline state exists for a step (e.g., 3-hydroxybutanoyl-CoA on 1F0Y, proton/hydride flight, NADH leave), the pose is drawn schematically and labeled as such in the narration. Occupancy is NAD⁺ + oxo product, not 3-hydroxy. Product-complex Å are not 3-hydroxy geomClaims.

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