D-β-hydroxybutyrate dehydrogenase - 3D Mechanism Simulator

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References & Databases

START HERE — how to read acetoacetate + NADH + H⁺ → (R)-3-hydroxybutanoate + NAD⁺ A D-β-hydroxybutyrate dehydrogenase cartoon on the fold analog that actually exists: 3W8E (1.24 Å X-ray) Alcaligenes faecalis BDH chain A with crystal NAD⁺ and D-3-hydroxybutyrate. Human BDH1 has no PDB — this is a species analog, not human BDH1. Occupancy is NAD⁺ + D-BHB, the ketogenesis products, not acetoacetate, not NADH — never read 3HR as acetoacetate. 3-OH on 3HR is atom O2 (on C3), not O3 (carboxylate). Acetoacetate is rebuilt on the 3HR pose [schematic]. His144 ★ on this analog is not UniProt human Tyr208 (Q02338 ACT_SITE 208 is Tyr, not His208). Gold is H⁺ onto the oxo oxygen. Blue is hydride NADH C4N → C3 (nicotinamide C4; adenine C4A is a different atom). NAD is a co-substrate and leaves as NAD⁺, not a prosthetic. BDH2 is another gene. NA is named, not catalytic. Acetone is non-enzymatic decarboxylation of acetoacetate — Overview only. Cite RCSB 3W8E; the primary citation is To be Published (no PMID). Measured Å are deposited 3W8E product-complex pairs only.
Crystal / X-ray structures PDB 3W8E — A. faecalis BDH + NAD⁺ + D-3-hydroxybutyrate + Na⁺, 1.24 Å X-ray (Kanazawa et al., To be Published). Coordinates are public. Occupancy is NAD⁺ + D-BHB. Human BDH1 UniProt Q02338 has no PDB. PDB 3VDR is the same protein + NAD + D-BHB at lower resolution — companion, not this mesh.
Mechanism — His144 analog proton; hydride NADH C4N → C3 UniProt Q02338 EC 1.1.1.30 writes the dehydrogenase direction (hydroxy + NAD⁺ = acetoacetate + NADH). This page teaches ketogenesis (acetoacetate → D-BHB). On this analog the catalytic histidine is His144 (UniProt Q02338 ACT_SITE 208 is Tyr208, not His208). Nicotinamide C4 is atom C4N. BDH2 is another gene. HADH is the opposite stereochemistry on a CoA thioester — a different gene. Source: UniProt Q02338 · RCSB 3W8E
0 — Setup: empty dehydrogenase pocket 3W8E occupancy is NAD⁺ + D-3-hydroxybutyrate (ketogenesis products). The pocket is shown empty so binding can start. Opaque, run:null (no autoplay). His144 ★ is the analog catalytic histidine (UniProt Q02338 ACT_SITE 208 is Tyr208, not His208). Human BDH1 has no PDB. 3-OH on 3HR is O2, not O3. BDH2 is another gene. NA is named, not catalytic.Source: PDB 3W8E (1.24 Å X-ray)
① — NADH binds Crystal NAD docks into the Rossmann pocket — deposited 3W8E occupancy is NAD⁺, the ketogenesis product. Teaching NADH is [schematic] on that pose. NAD is a co-substrate, not a prosthetic (it will leave as NAD⁺). Nicotinamide C4 is atom C4N; adenine C4A is a different atom. Human BDH1 has no PDB.Source: PDB 3W8E NAD pose
② — Acetoacetate binds [schematic] Acetoacetate docks on the 3W8E 3HR pose — not a deposited oxo. 3HR on 3W8E is (R)-3-hydroxybutanoate (D-BHB product), not acetoacetate. 3-OH on 3HR is atom O2 (C3), not O3 (carboxylate). Product-complex Å are not acetoacetate geomClaims.Source: 3W8E 3HR pose rebuilt as acetoacetate
③ — His144 protonates the oxo oxygen (hypothetical, lit.-based) Gold H⁺ rides from His144 ND1 onto acetoacetate O2. On this analog the atom is PDB His144 (UniProt Q02338 ACT_SITE 208 is Tyr208, not His208). Tyr155 / Ser142 are named. Gold = H⁺. Product-complex O2 distances are not acetoacetate geomClaims. Human BDH1 has no PDB.Source: compiled BDH His · UniProt Q02338 · 3W8E His144
④ — Hydride NADH C4N → C3 → D-BHB + NAD⁺ (hypothetical, lit.-based) Blue hydride rides from NAD C4N (nicotinamide C4; adenine C4A is a different atom) onto acetoacetate C3. Acetoacetate cross-fades in place to crystal D-3-hydroxybutyrate. NAD relabels NAD⁺ and will leave — co-substrate, not prosthetic. 3HR C3 ⋯ NAD C4N = 3.06 Å is deposited 3W8E product complex. Slow-motion on purpose. Blue = hydride, not oxygen nucleophile. Human BDH1 has no PDB.Source: compiled BDH hydride · 3W8E NAD/3HR
⑤ — D-BHB and NAD⁺ leave — circulating ketone D-3-hydroxybutyrate and NAD⁺ depart in opposite directions. NAD is a co-substrate, not a prosthetic. Teaching product is circulating D-BHB. Acetone is non-enzymatic decarboxylation of acetoacetate — not this page. This page does not run BDH2 and is not OXCT1 ketolysis. Product-complex Å are not acetoacetate geomClaims. Human BDH1 has no PDB.Source: ketogenesis bookkeeping · EC 1.1.1.30

How to read this page — a first-pass primer First pass: Setup (empty pocket, His144 ★, analog not human, occupancy is NAD⁺ + D-BHB) → ① schematic NADH docks on NAD pose → ② schematic acetoacetate docks on 3HR pose → ③ gold H⁺ His144 → oxo O2 → ④ blue hydride NADH C4N → C3, fade to D-BHB, NAD⁺ → ⑤ D-BHB and NAD⁺ leave opposite; circulating ketone. Second pass: 3.06 / 2.54 / 2.66 / 3.63 Å are crystal facts on 3W8E product complex; acetoacetate is [schematic]; 3HR is D-BHB product, not substrate. 3-OH is O2, not O3. Third pass: open “Disagreements” for product occupancy vs acetoacetate, analog His144 vs UniProt Tyr208 (not His208), and BDH2 vs this gene.
Chemistry primer — NAD-dependent D-hydroxy reduction BDH1 reduces acetoacetate to D-β-hydroxybutyrate with NADH. Teaching direction is ketogenesis (oxo → D-hydroxy). His144 analog donates H⁺ onto the oxo oxygen; the C3 hydride comes from NADH C4N. NAD is a co-substrate and leaves as NAD⁺. Gold is H⁺. Blue is hydride, not oxygen nucleophile. This is not BDH2 (cytosolic SDR) and not HADH (3S on a CoA thioester). Acetone is non-enzymatic.
Words used on screen — analog mesh · product occupancy · His144 ★ · O2 not O3 · C4N Analog mesh — 3W8E is A. faecalis; human BDH1 has no PDB. Product occupancy — 3W8E holds NAD⁺ + D-BHB, the ketogenesis products. His144 ★ — PDB id on this analog; UniProt Q02338 ACT_SITE 208 is Tyr208, not His208. O2 not O3 — 3-OH is O2 on C3; O3 is a carboxylate oxygen on C1. C4N — nicotinamide C4 on this mesh; adenine C4A is a different atom.

Legend & Fidelity

Mechanism fidelity — measured vs. inferred The measured layer: 3W8E (1.24 Å X-ray) A. faecalis BDH + NAD⁺ + D-3-hydroxybutyrate; 3HR C3 ⋯ NAD C4N = 3.06 Å; Ser142 OG ⋯ 3HR O2 = 2.54 Å; Tyr155 OH ⋯ 3HR O2 = 2.66 Å; His144 ND1 ⋯ 3HR O2 = 3.63 Å. The inferred layer ([schematic]): acetoacetate rebuilt on the 3HR pose, NADH on the NAD pose, transferring H⁺ / hydride spheres, NAD→NAD⁺ relabel, product leave. Binding order is compiled staging, not a kinetic fit. The protein mesh is static. Product-complex Å are not acetoacetate geomClaims. 3HR is D-BHB product, not substrate. Human BDH1 has no PDB.
Disagreements on record (a) Occupancy vs substrate. 3W8E holds NAD⁺ + D-3-hydroxybutyrate (ketogenesis products), not acetoacetate, not NADH. (b) Species. This mesh is A. faecalis. Human BDH1 has no PDB. (c) Numbering. Screen ★ is His144 (this analog). UniProt Q02338 ACT_SITE 208 is Tyr208, not His208. (d) 3-OH atom. 3HR 3-OH is O2, not O3 (carboxylate). (e) Product-complex Å are not acetoacetate geomClaims. (f) Concerted vs split proton/hydride — this page splits ③ then ④ for 1-event/1-step teaching. (g) BDH2 (cytosolic SDR) is another gene. (h) HADH is opposite stereochemistry on a CoA thioester — a different gene. (i) Phosphatidylcholine allosteric requirement is Regulation, not motion. (j) Human transit 1–46 is not this analog mesh (Cα 1–260). (k) 3VDR is a lower-res companion. (l) Acetone is non-enzymatic, not this page. (m) OXCT1 is ketolysis, not this path. (n) 3W8E primary citation is To be Published — no PMID.
Regulation — isoforms · phosphatidylcholine · matrix This reduction is mitochondrial BDH1 only. Cytosolic BDH2 is another gene — not this mesh. Human BDH1 requires phosphatidylcholine as an allosteric activator — named here, not animated. Matrix localization is assumed, not a catalytic event on this page. Human BDH1 has no PDB — this cartoon is the A. faecalis analog.Source: UniProt Q02338 · PDB 3W8E
Kinetics scope (no measured timecourse on this page) One acetoacetate + NADH + H⁺ → (R)-3-hydroxybutanoate + NAD⁺ event is drawn, not a steady-state run. Compiled BRENDA values for EC 1.1.1.30 are not re-asserted here — no measured k_cat/K_m on this page [schematic]. Pair with a kinetics chapter.Source: BRENDA EC 1.1.1.30 — no k_cat/K_m re-asserted
Sequence Human BDH1 UniProt Q02338 · NCBI Gene 622. This screen uses 3W8E analog numbering (His144 ≠ UniProt Tyr208 (not His208)). Chain A. Cα 1–260. Human transit 1–46 is not this analog mesh.
Simulation map — what you see is what is written Setup = 3W8E pocket empty (opaque, no autoplay). ① schematic NADH moves in on NAD pose. ② schematic acetoacetate moves in on 3HR pose. ③ gold H⁺ His144 → oxo O2. ④ slow-mo: blue hydride NADH C4N → C3; acetoacetate fades to D-BHB; NAD relabels NAD⁺. ⑤ D-BHB and NAD⁺ leave opposite. Only these events move.
Sources — bibliography of this page S1 — PDB 3W8E: A. faecalis BDH + NAD⁺ + D-3-hydroxybutyrate, 1.24 Å X-ray — public coordinates; measured 3HR C3⋯NAD C4N = 3.06 Å · Ser142 OG⋯3HR O2 = 2.54 Å · Tyr155 OH⋯3HR O2 = 2.66 Å · His144 ND1⋯3HR O2 = 3.63 Å. Primary citation To be Published — no PMID S2 — Companion PDB 3VDR — same protein + NAD + D-BHB, lower resolution, not this mesh S3 — Sequence: UniProt Q02338 · NCBI Gene 622 — human BDH1 has no PDB S4 — Kinetics: BRENDA EC 1.1.1.30 — no k_cat/K_m re-asserted on this page

› Backbones and NAD / 3HR poses are taken directly from the listed PDB entries, superposed into one common frame. Where no crystalline state exists for a step (e.g., acetoacetate on 3W8E, NADH, proton/hydride flight, NAD⁺ leave), the pose is drawn schematically and labeled as such in the narration. Occupancy is NAD⁺ + D-BHB product, not acetoacetate. Product-complex Å are not acetoacetate geomClaims. Human BDH1 has no PDB.

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