Succinate Dehydrogenase - 3D Mechanism Simulator

Loading structural data… (1ZOY)

References & Databases

START HERE — how to read succinate → fumarate + QH₂ This page is TCA step 6 and ETC Complex II on one flavoprotein slice. Real crystal: porcine mitochondrial Complex II 1ZOY with FAD covalently tethered as 8α-N3-histidyl-FAD to His57. Transferring H is schematic (the crystal has no H mesh): gold H⁺ parks on His365 ★ in step ②; blue hydride H⁻ (ball + arrow) goes to FAD N5 in step ③ and FAD relabels FADH⁻ (N5-H only); step ④ (proposal) adds N1-H to make FADH₂. Step ⑥ is an educational Fe-S path marker — no Fe-S or Q coordinates are in this Fp slice, and no Å is claimed for those hops. FAD never leaves.
Crystal structure PDB 1ZOY — porcine heart mitochondrial Complex II (succinate:ubiquinone oxidoreductase), 2.4 Å, Sun F et al., Cell 2005, PMID:15989954 · DOI:10.1016/j.cell.2005.05.025. Flavoprotein (Fp) subunit with covalently bound FAD shown here. The iron–sulfur protein, membrane anchors (CybL/CybS, heme b), and Q site were not extracted. Related deposit 1ZP0 (3.5 Å) binds the succinate analog 3-nitropropionate plus the Q-site inhibitor TTFA — named, not drawn.
Mechanism — His57 tether · His365 ★ · hydride to N5 · Fe-S → Q His57 covalently links FAD (NE2⋯C8M = 1.71 Å). His365 ★ is the general base at the isoalloxazine edge (NE2⋯N5 = 4.97 Å, FAD-relative; no substrate Å is claimed). Arg409 grips the dicarboxylate (NH2⋯N5 = 5.25 Å). The C3 hydride goes to FAD N5 (FADH⁻); a proposal proton at N1 completes FADH₂; electrons then travel 2Fe-2S → 4Fe-4S → 3Fe-4S → ubiquinone. Source: Sun et al. 2005 (PMID:15989954) · Mäkelä et al. 2014 (PMID:25342163) · Yankovskaya et al. 2003 (PMID:12560550), Science (1NEK family, Fe-S order)
0 — Setup: covalent FAD at the flavoprotein The deposited Fp holds FAD as 8α-N3-histidyl-FAD on His57. Opaque, run:null. His365 ★ and Arg409 line the flavin edge. Fe-S clusters and Q are not in this slice.Source: PDB 1ZOY (2.4 Å), Sun 2005
① — Succinate binds beside N5 [schematic] Succinate enters the dicarboxylate pocket. Arg409 organizes one carboxylate; C2/C3 sit at the flavin edge. No succinate co-crystal is in 1ZOY — this seat is schematic, and no substrate Å is claimed.Source: schematic pose (no succinate co-structure in 1ZOY) · Arg409 grip from Sun 2005 / Mäkelä 2014
② — His365 takes the C2 proton His365 ★ abstracts the C2 proton. A gold H⁺ sphere rides with a gold arrow from substrate C2 to His365 NE2 (the proton moves toward the base). Slow on purpose — the flight fills the step. The enzyme keeps this proton parked on NE2 as His-H⁺ — it is not absorbed. Net bookkeeping to FAD N1 is the next proposal step.Source: His-base assignment, Mäkelä 2014 · 1ZOY His365⋯N5 = 4.97 Å (FAD-relative)
③ — Hydride to FAD N5 → fumarate [schematic] (hypothetical, lit.-based order) The C3 hydride H⁻ (blue ball + blue arrow) rides from substrate C3 onto FAD N5 — hydrogen plus two electrons. Arrow ends sit on those atoms; the curve bows toward the camera. Succinate cross-fades in place to fumarate (trans C=C; H not drawn). FAD relabels FADH⁻ (N5-H only — one proton short of FADH₂). Concerted proton+hydride in one throw is the opposing view (Disagreements). Slow-motion on purpose.Source: hydride → N5, Mäkelä 2014 · Yankovskaya 2003 (PMID:12560550)
④ — Parked H⁺ completes FADH₂ at N1 [schematic] (hypothetical, lit.-based) The parked gold H⁺ leaves His365 NE2 for FAD N1 (ball + arrow together). Slow on purpose. FADH⁻ (N5-H) plus this N1-H is FADH₂. The opposing view parks this proton on solvent instead of His.Source: FADH₂ N5-H + N1-H bookkeeping (flavoprotein literature); His-vs-solvent = proposal
⑤ — Fumarate released — FAD stays [schematic] Fumarate leaves for fumarase (TCA step 7). Covalent FAD stays as FADH₂ — the 8α-histidyl tether does not undock. Electrons have not yet reached the Q pool.Source: covalent 8α-N3-histidyl-FAD, Sun 2005 / Mäkelä 2014; separate product exit
⑥ — e⁻ wire — FADH₂ → 2Fe-2S → 4Fe-4S → 3Fe-4S → QH₂ [schematic] An educational path marker hops one cluster at a time. No Fe-S or Q coordinates are in this Fp slice — no Å is claimed. QH₂ needs two electrons and two protons; this hop sequence is compressed teaching, not two N3 visits or a drawn Q-site proton path. Complex I is bypassed; ≈1.5 ATP per FADH₂ is a literature P/O, not this simulator’s output. Onward: ETC overview. FADH₂ relabels back to FAD.Source: Fe-S order, Yankovskaya et al. 2003 (PMID:12560550) · Q pool / CI bypass, textbook OXPHOS

How to read this page — a first-pass primer First pass (ignore the noise): watch the order — Setup (covalent FAD on His57) → ① succinate docks beside N5 → ② gold H⁺ parks on His365 → ③ blue hydride H⁻ flies C3 → N5 (succinate → fumarate; FAD → FADH⁻) → ④ the parked proton completes FADH₂ at N1 (proposal) → ⑤ fumarate leaves → ⑥ one hop at a time FADH₂ → 2Fe-2S → 4Fe-4S → 3Fe-4S → QH₂. Second pass (the numbers): only three Å are crystal facts, all FAD-relative — His57⋯C8M 1.71, His365⋯N5 4.97, Arg409⋯N5 5.25. No substrate Å. Third pass: open “Mechanism fidelity” and “Disagreements” to separate measured geometry from the literature-based reconstruction.
Chemistry primer — hydride vs proton, FADH⁻ vs FADH₂ Succinate is a four-carbon dicarboxylate. This page’s C2/C3 labels are the two methylene carbons of that chain (not a universal PDB atom map — 1ZOY has no succinate). His365 takes a proton H⁺ from C2 (gold). C3 then donates a hydride H⁻ to FAD N5 (blue) — hydrogen plus two electrons — making trans-fumarate and the flavin anion FADH⁻ (N5-H). Neutral FADH₂ is N5-H plus N1-H; step ④ is that second proton as a proposal. The gold/blue balls are trajectory cartoons, not curly-arrow electron pushing. Net flavin site: succinate + FAD → fumarate + FADH₂. Net enzyme: succinate + Q ⇄ fumarate + QH₂.
Words used on screen — trans dehydrogenation · FADH⁻ · Q pool Trans dehydrogenation — the two hydrogens leave from opposite faces of the C2–C3 bond, giving trans-fumarate. FADH⁻ — the N5-H flavin anion after hydride arrival; one proton short of FADH₂. Q pool — membrane ubiquinone/ubiquinol that Complex III oxidizes; Complex II feeds it without pumping at Complex I. 8α-N3-histidyl-FAD — FAD’s 8-methyl carbon is covalently attached to His57 NE2; the cofactor does not undock.

Legend & Fidelity

Mechanism fidelity — measured vs. inferred The measured layer: the 1ZOY Fp frame (2.4 Å) with covalent FAD, and three contacts reproduced from those coordinates — His57 NE2⋯FAD C8M 1.71 Å, His365 NE2⋯FAD N5 4.97 Å, Arg409 NH2⋯FAD N5 5.25 Å. These are FAD-relative crystal numbers, never substrate distances. The inferred layer (all [schematic]): succinate/fumarate poses (no co-crystal on 1ZOY; 1ZP0 binds 3-nitropropionate, not succinate), the ②–④ proton/hydride order, FADH⁻ vs FADH₂ bookkeeping, parked H⁺ → N1, and the ⑥ Fe-S/Q hops. Asp233 sits 20.17 Å from N5 in this frame and is not pinned — pocket-organization text only.
Disagreements on record (a) ②/③ concerted vs stepwise. The screen splits proton and hydride (one event per step); a concerted throw is the opposing view and is not drawn. (b) N1 proton His vs solvent. Step ④ is a proposal chip — some accounts park the second proton on solvent. (c) Q-site geometry varies by species and is absent from this Fp slice, so no Å is claimed. (d) C2 vs C3 numbering. Older reviews sometimes call the hydride carbon “C1”; this page uses succinate C2 (proton) / C3 (hydride) as teaching labels on a schematic pose. (e) QH₂ bookkeeping. Ubiquinol needs 2 e⁻ + 2 H⁺; step ⑥ compresses that into one hop sequence — not two N3 visits and not a drawn Q-site proton path.
Dual identity — TCA 6 and Complex II Succinate → fumarate is TCA step 6. The same enzyme is ETC Complex II (succinate:ubiquinone oxidoreductase, EC 1.3.5.1): FADH₂ electrons enter the membrane Q pool as QH₂, bypassing Complex I (no H⁺ pumping at CI). ≈1.5 ATP per FADH₂ vs ≈2.5 per NADH is a compiled literature P/O, not this page’s output. Onward: ETC overview · Complex I/III/IV/V pages.
Kinetics scope (no measured timecourse on this page) One succinate → fumarate + QH₂ event is drawn, not a steady-state run. Compiled BRENDA values for EC 1.3.5.1 are not re-asserted here — no measured k_cat/K_m on this page [schematic]. Pair with a kinetics chapter.
Regulation — OAA · malonate · SDHx Oxaloacetate is a tight inhibitor of mammalian SDH. Malonate is the classic competitive analog of succinate. SDH subunit genes (SDHA/B/C/D) are tumor-suppressor loci (hereditary paraganglioma / pheochromocytoma) — named in text, not drawn as mutant structures.Source: textbook SDH regulation · SDHx tumor-suppressor genetics (named, not simulated)
Simulation map — what you see is what is written Setup = 1ZOY Fp + covalent FAD (opaque, run:null). ① succinate moves in (schematic) beside N5. ② gold H⁺ + gold arrow C2 → His365 NE2 (slow flight fills the step); proton stays parked. ③ STAR slow-mo: blue hydride H⁻ + blue arrow C3 → N5 (ends on those atoms); succinate fades to fumarate; FAD relabels FADH⁻; parked gold H⁺ remains on His365. ④ proposal: parked gold H⁺ + gold arrow His365 → FAD N1 (slow); FADH⁻ relabels FADH₂. ⑤ fumarate leaves; FAD stays. ⑥ STAR: one hop at a time FADH₂ → 2Fe-2S → 4Fe-4S → 3Fe-4S → Q → QH₂; FADH₂ relabels FAD. Only these events move.
Sequence Pig SDHA (flavoprotein) UniProt Q0QF01 · SDHB (iron-sulfur) UniProt Q007T0 · NCBI Gene 396677 (SDHA). Screen uses 1ZOY PDB-author numbering (His57 / His365 / Arg409 = as deposited; SIFTS maps author = display).
Sources — bibliography of this page S1 — Kinetics: BRENDA EC 1.3.5.1 — no k_cat/K_m re-asserted on this page S2 — Sequence: UniProt Q0QF01 (SDHA) · Q007T0 (SDHB) · NCBI Gene 396677 S3 — PDB 1ZOY (2.4 Å): porcine mito Complex II Fp + covalent FAD; Sun et al. 2005, Cell 121:1043–1057, PMID:15989954 · DOI:10.1016/j.cell.2005.05.025. Related: 1ZP0 (3.5 Å, 3-nitropropionate + TTFA — named, not drawn) S4 — Mäkelä et al. 2014, Biochem Soc Trans, PMID:25342163 — covalent 8α-N3-histidyl-FAD; His base; hydride to N5; Fe-S to UQ S5 — Yankovskaya et al. 2003, Science 299:700–704, PMID:12560550 · DOI:10.1126/science.1079605 (PDB 1NEK family) — trans dehydrogenation, FAD N5 hydride, Fe-S order 2Fe-2S → 4Fe-4S → 3Fe-4S → Q

› Backbones and ligand poses are taken directly from the listed PDB entries, superposed into one common frame. Where no crystalline state exists for a step (e.g., succinate approach, fumarate release, Fe-S/Q hops), the pose is drawn schematically and labeled as such in the narration.

FAD-binding domainC-terminal domainONP