Complex I — NADH:ubiquinone oxidoreductase

Loading structural data… (4HEA Complex I)

References & Databases

Frame — 4HEA, Thermus thermophilus Complex I Respiratory Complex I (NADH:ubiquinone oxidoreductase) from Thermus thermophilus — PDB 4HEA. The 3D backbone, FMN, and eight Fe-S clusters are deposited coordinates. Residue numbers follow 4HEA PDB-author numbering. This is a bacterial crystal, not bovine or human CI — disclosed under organism mixing.Source: PDB 4HEA (Baradaran et al. 2013, Nature · DOI:10.1038/nature11871)
Overall reaction NADH + Q + 5 H⁺(N) → NAD⁺ + QH₂ + 4 H⁺(P). EC 7.1.1.2. Four protons are pumped per two electrons. The Q-reduction / pump coupling model is a literature proposal — see ⑥.Source: BRENDA EC 7.1.1.2 · pumping proposal: Baradaran 2013
Setup — FMN + Fe-S wire, pockets empty (real 4HEA) Setup shows the real FMN and eight Fe-S clusters with both substrate pockets empty. Cluster N1a is labeled “off path” and drawn dim: it is a dead-end next to FMN, not on the electron wire.Source: PDB 4HEA (Baradaran et al. 2013) — N1a off the FMN→N2 wire
① — NADH arrives at FMN [schematic] Nicotinamide cartoon of NADH (C4 + carboxamide, ribose–phosphate stub — not the full dinucleotide) docks so C4 faces FMN N5. No NADH is co-crystallized in this 4HEA slice. Docking only — hydride transfer is ③. NADH before Q is teaching order, not a kinetic mechanism.Source: registered schematic — no NADH ligand in this 4HEA slice; C4 toward N5 per Baradaran et al. 2013
② — Q arrives at cluster N2 [schematic] Benzoquinone cartoon of Q (two carbonyls, two methoxy, short isoprene stub — not the C₁₀ tail) docks in the N2 cavity. 4HEA in this data slice has no deposited Q ligand; the Q headgroup in the Nature paper sits ~12 Å from N2 with Tyr87/His38 H-bonds (bacterial numbering) — that contact is text-only here, not a measured claim on this seat.Source: registered schematic — no Q ligand in this slice; ~12 Å / Tyr87·His38 is literature text from Baradaran et al. 2013, not re-measured here
③ — Hydride transfer — NADH C4 → FMN N5 [schematic] One hydride H⁻ (blue bead + blue arrow) rides from NADH C4 to FMN N5. A hydride is two electrons plus a proton. NADH cross-fades in place to NAD⁺ (C4 hydride gone). Slow-mo on the transfer window. The Fe-S wire does not move in this step — those clusters are one-electron carriers.Source: proposal pose — hydride C4→N5 per Baradaran et al. 2013; no TS deposited
④ — e⁻ wire — FMN → N3 → N1b → N4 → N5 → N6a → N6b → N2 An educational path marker rides cluster by cluster in the literature order. Fe-S clusters carry one electron. The bead is not a physical particle; real transfer is distance-dependent tunneling, not marble-rolling. One hop at a time so the order is readable. N1a is not in this sequence. Nearest Fe–Fe from 4HEA: FMN N5–N3 10.54 Å; N3–N1b 15.41 Å; N1b–N4 10.47 Å; N4–N5 27.64 Å; N5–N6a 35.49 Å; N6a–N6b 9.33 Å; N6b–N2 11.11 Å. Off-path N3–N1a 20.95 Å.Source: path: Baradaran et al. 2013 · Fe–Fe re-measured from PDB 4HEA
⑤ — N2 reduces Q → QH₂ [schematic] After the wire, a path marker rides from N2 onto a carbonyl oxygen of docked Q. Q cross-fades in place to QH₂ (phenols appear). QH₂ needs two electrons and two protons — this fade compresses that bookkeeping into one teaching beat after a one-electron wire. It is not two separate N2 visits packed on screen.Source: registered schematic — Q reduction at N2 per Baradaran et al. 2013; no Q ligand in this slice
⑥ — 4 H⁺ to the P-side PROPOSAL [schematic] (hypothetical, lit.-based). Four protons are shown moving toward the P-side. Pumping is coupled to Q reduction via membrane-arm conformational change — not electrons and protons flying together. Alternative coupling models exist; none is drawn as fact. The protein mesh is static, so helix motion of the membrane arm is not simulated.Source: proposal — no deposited pump trajectory; coupling discussed in Baradaran et al. 2013 and Brandt 2006
⑦ — NAD⁺ and QH₂ depart (two directions) [schematic] NAD⁺ returns to the matrix; QH₂ leaves through the membrane toward Complex III. Two products, two directions. Complex III chemistry lives on the CIII page; Complex II (SDH) is a separate simulator (sdh.html).Source: display convention — separate exits; no external geometry claimed · CIII etcc3.html

Legend & Fidelity

Mechanism fidelity — measured vs. inferred Measured layer: protein Cα, FMN, eight Fe-S clusters, NADH-pocket residues (4HEA). Inferred layer: NADH nicotinamide / Q benzoquinone cartoons, hydride and e⁻ beads riding the hop path with the arrow (electrons are not particles on a wire — educational), H⁺ spheres and pump direction. Å numbers on this page are nearest-Fe distances between deposited clusters, not schematic seats. NADH→FMN is a hydride (2 e⁻); Fe-S hops are one-electron; the Q→QH₂ fade is compressed bookkeeping, not a second N2 visit.
Why are NADH and Q “[schematic]”? This 4HEA data slice contains FMN and Fe-S ligands, not NADH or ubiquinone. Substrate poses are literature-based reconstructions at the FMN N5 face and the N2 cavity and are labeled [schematic]. No Å is claimed for those seats.Source: PDB 4HEA ligands = FMN + Fe-S only
The protein mesh is static No membrane-arm helix motion, no thermal sampling. The H⁺ pump is a schematic overlay, not a conformational movie.
Physiological regulation Mammalian Complex I is inhibited by rotenone and piericidin A at the Q site; reverse electron transport can generate ROS at FMN. This page does not animate inhibitors or ROS. Bacterial 4HEA is the structural frame — mammalian regulation is named, not drawn. See Brandt, Annu Rev Biochem 2006 (PMID:16756498).
Kinetics scope This tool animates one catalytic event; it does not model timecourses, steady-state kinetics, or Km / kcat / Vmax. Compiled human/bovine CI turnover is order-10² s⁻¹ in the literature and is not re-measured here — see BRENDA EC 7.1.1.2. Pair with a kinetics chapter. NADH/Q binding order is not asserted as a kinetic mechanism on screen (arrival order is educational staging).
Sequence T. thermophilus Nqo1 / NuoF (51 kDa FMN subunit, 4HEA entity 1, 438 aa) UniProt Q56222 (SIFTS) · NCBI taxonomy 300852 (HB8). Frame numbering = 4HEA PDB-author, not a mammalian CI gene.
Sources — bibliography of this page S1 — PDB 4HEA: T. thermophilus Complex I; Baradaran et al. 2013, Nature 494:443–448, PMID:23417064, DOI 10.1038/nature11871 (RCSB primary citation) S2 — BRENDA EC 7.1.1.2 (compiled turnover order-10² s⁻¹; not re-measured here) S3 — Brandt 2006, Annu Rev Biochem, PMID:16756498 (mammalian CI regulation named, not drawn) S4 — UniProt Q56222 (Nqo1/NuoF, SIFTS on 4HEA entity 1) · NCBI taxonomy 300852 S5 — How this page is drawn: NADH/Q/QH₂/H⁺ = [schematic]; N1a off-path; ⑥ pump = PROPOSAL; Fe–Fe Å from deposited 4HEA clusters only (not schematic seats); NADH→FMN hydride (2 e⁻) vs Fe-S one-electron hops vs QH₂ two-electron bookkeeping are labeled on ③–⑤

› The 3D protein is real 4HEA Complex I with genuine FMN and Fe-S clusters. NADH, Q, QH₂ and H⁺ are compact schematic molecules posed at the pockets and labeled [schematic]. N1a is off the electron path.

Complex I (4HEA)ONPS