Carnitine palmitoyltransferase 1A - 3D Mechanism Simulator

Loading structural data… (1NM8)

References & Databases

START HERE — how to read palmitoyl-CoA + carnitine → palmitoylcarnitine + CoA A carnitine-acyltransferase cartoon on the human CRAT frame that actually exists: 1NM8 (1.60 Å) apo chain A. Human CPT1A (P50416) catalytic domain has no PDB — fold analog / gene hedge. Palmitoyl-CoA, CoA-SH, and palmitoylcarnitine are [schematic]. L-carnitine pose is a 1S5O overlay [schematic], not a deposited ternary on 1NM8. His322 ★ on this mesh is CRAT UniProt His343 ≅ CPT1A His473 (compiled; H473A loss is CPT1A literature, not a CRAT crystal fact). No covalent residue intermediate (A-page). Gold is H⁺. Blue is oxygen nucleophile, not hydride. Measured Å are deposited 1NM8 pairs only. Overlay Å are not geomClaims. Malonyl-CoA gating is 2LE3 N-term, not this pocket. CPT1B/C are other genes.
Crystal structures PDB 1NM8 — human carnitine acetyltransferase, 1.60 Å, apo (Wu et al. 2003). Coordinates are public. This is CRAT (P43155), not CPT1A. 1S5O is the same protein + L-carnitine, 1.80 Å — named overlay, not this ternary. 2LE3 is CPT1A N-terminus 1–42 NMR (malonyl-CoA switch; Rao et al., J Biol Chem 2011, PMID:21990363) — regulation only, not this fold. Human CPT1A UniProt P50416 has no catalytic-domain PDB.
Mechanism — carnitine transesterification UniProt P50416 EC 2.3.1.21: palmitoyl-CoA + L-carnitine → palmitoylcarnitine + CoA. His473 is the compiled proton acceptor on CPT1A (H473A loss, PMID:11553629). On this mesh the catalytic histidine is CRAT His322. Succinyltransferase EC 2.3.1.- is not shown. Source: UniProt P50416 · Wu et al. 2003 · Morillas et al. 2001
0 — Setup: empty CRAT pocket 1NM8 is apo (HOH only). The pocket is shown empty so ordered binding can start. Opaque, run:null (no autoplay). Human CPT1A has no catalytic PDB; this mesh is CRAT. His322 ★ is the catalytic histidine on this frame.Source: PDB 1NM8 (1.60 Å)
① — Palmitoyl-CoA binds [schematic] Palmitoyl-CoA docks with the thioester carbonyl toward carnitine O3 / His322. Not deposited on apo 1NM8. Teaching chain is palmitate. CPT1B/C are other genes.Source: schematic palmitoyl-CoA on 1NM8 His322
② — L-carnitine binds [schematic] L-carnitine docks from a 1S5O overlay onto this 1NM8 apo mesh — not a deposited ternary. His322 NE2 ⋯ Tyr320 OH = 3.73 Å is deposited 1NM8. Overlay carnitine distances are not geomClaims.Source: 1NM8 His322/Tyr320; 1S5O named overlay
③ — His322 takes the carnitine OH proton (hypothetical, lit.-based) Gold H⁺ rides from carnitine 3-OH to His322 NE2. On this mesh the atom is CRAT His322 (UniProt His343). CPT1A His473 is compiled; H473A loss is CPT1A literature. His322 NE2 ⋯ Glu326 OE1 = 3.98 Å.Source: compiled CPT His · Morillas et al. 2001 PMID:11553629 · 1NM8 His322/Glu326
④ — Carnitine-O attacks carbonyl → acylcarnitine + CoA (hypothetical, lit.-based) Blue nucleophile rides from carnitine 3-O to the palmitoyl-CoA carbonyl. Palmitoyl-CoA + carnitine fade in place to schematic palmitoylcarnitine and schematic CoA-SH. CoA thiolate reprotonation (His regeneration) is not drawn. A-page. Slow-motion on purpose.Source: compiled carnitine acyltransferase · UniProt P50416
⑤ — Acylcarnitine and CoA leave — CACT next [schematic] Palmitoylcarnitine and CoA-SH depart opposite ways. Teaching product is C16 palmitoylcarnitine. CACT (next) antiports this cargo — CACT is a carrier, not an enzyme. This page does not antiport across the IMM. Malonyl-CoA gating is 2LE3 N-term, not this pocket.Source: β-oxidation bookkeeping · EC 2.3.1.21

How to read this page — a first-pass primer First pass: Setup (empty CRAT pocket, His322 ★, fold analog) → ① schematic palmitoyl-CoA docks → ② schematic L-carnitine docks → ③ gold H⁺ carnitine-OH → His322 → ④ blue carnitine-O → carbonyl, fade to acylcarnitine + CoA → ⑤ acylcarnitine and CoA leave opposite ways; CACT next (C16 cargo; CACT is a carrier). Second pass: 3.73 / 3.98 / 4.16 Å are crystal facts on 1NM8; palmitoyl-CoA, carnitine pose, CoA, and acylcarnitine are [schematic]. Teaching product is C16. Third pass: open “Disagreements” for CRAT ≠ CPT1A, His322 vs His473, 1S5O overlay vs this ternary, and 2LE3 N-term vs this fold.
Chemistry primer — carnitine transesterification CPT1A on the outer mitochondrial membrane transfers the acyl chain from CoA to carnitine so the ester can enter the matrix via CACT. Teaching product is C16 palmitoylcarnitine. CACT (next) is a carrier, not an enzyme — it antiports that cargo. His473 (this screen: CRAT His322) is the compiled general base that takes the carnitine 3-OH proton; the deprotonated oxygen attacks the thioester carbonyl; CoA-SH leaves. Gold is H⁺. Blue is oxygen nucleophile, not hydride. This is not CACT (antiport) and not CPT1B/C.
Words used on screen — fold analog · overlay · His322 ★ Fold analog — the mesh is human CRAT; CPT1A catalytic domain has no PDB. Overlay — 1S5O L-carnitine is a different crystal seated by Kabsch, not deposited on 1NM8. His322 ★ — PDB id on this CRAT frame; UniProt CRAT His343 ≅ CPT1A His473 in the drawer. CoA stub — pantetheine cartoon, not full 3′-phospho-ADP-CoA.

Legend & Fidelity

Mechanism fidelity — measured vs. inferred The measured layer: 1NM8 (1.60 Å) human CRAT apo; His322 NE2 ⋯ Tyr320 OH = 3.73 Å; His322 NE2 ⋯ Glu326 OE1 = 3.98 Å; His322 NE2 ⋯ Tyr86 OH = 4.16 Å. The inferred layer ([schematic]): palmitoyl-CoA, 1S5O carnitine overlay, CoA-SH stub, palmitoylcarnitine, transferring H⁺ / nucleophile spheres, product leave. Binding order is compiled staging, not a kinetic fit. The protein mesh is static. Overlay carnitine Å are not geomClaims.
Disagreements on record (a) Gene. 1NM8 is CRAT (P43155), not CPT1A (P50416). CPT1A catalytic domain has no PDB. (b) His numbering. Screen ★ is His322 (PDB). UniProt CRAT His343 ≅ CPT1A His473; H473A loss is CPT1A literature, not a CRAT crystal fact. (c) 1S5O vs 1NM8. Carnitine is a different crystal; the pose on this mesh is overlay/[schematic]. (d) 2LE3 is N-terminus 1–42 NMR, not this catalytic fold. (e) CPT1B/C are other genes. (f) Succinyltransferase EC 2.3.1.- is not shown. (g) Concerted vs split proton/attack — this page splits ③ then ④ for 1-event/1-step teaching.
Regulation — malonyl-CoA · isoforms Malonyl-CoA inhibition is the physiological gate on CPT1A. That switch lives on the N-terminus (2LE3, residues 1–42), not this CRAT pocket. This mesh is liver CPT1A teaching. CPT1B (muscle) and CPT1C (brain) are other genes. Membrane anchor is not this cartoon.Source: UniProt P50416 · PDB 2LE3
Kinetics scope (no measured timecourse on this page) One palmitoyl-CoA + carnitine → palmitoylcarnitine + CoA event is drawn, not a steady-state run. Compiled BRENDA values for EC 2.3.1.21 are not re-asserted here — no measured k_cat/K_m on this page [schematic]. Pair with a kinetics chapter.Source: BRENDA EC 2.3.1.21 — no k_cat/K_m re-asserted
Sequence Human CPT1A UniProt P50416 · NCBI Gene 1374 (no catalytic-domain PDB). This screen uses human CRAT numbering (His322 on 1NM8; UniProt CRAT His343). Chain A. Cα 9–599.
Simulation map — what you see is what is written Setup = 1NM8 pocket empty (opaque, no autoplay). ① schematic palmitoyl-CoA moves in. ② schematic L-carnitine moves in. ③ gold H⁺ carnitine-OH → His322. ④ slow-mo: blue carnitine-O → carbonyl; palmitoyl-CoA+carnitine fade to acylcarnitine + CoA. ⑤ acylcarnitine and CoA leave opposite ways. Only these events move.
Sources — bibliography of this page S1 — PDB 1NM8: human CRAT, 1.60 Å, apo — public coordinates; measured NE2⋯Tyr320 OH = 3.73 Å · NE2⋯Glu326 OE1 = 3.98 Å · NE2⋯Tyr86 OH = 4.16 Å S2 — Wu et al., J Biol Chem 2003, PMID:12562770 — CRAT structure; companion 1S5O carnitine (PMID:15099582) S3 — Sequence: UniProt P50416 (human CPT1A, no catalytic PDB) · NCBI Gene 1374 · CRAT P43155 S4 — His473: Morillas et al., J Biol Chem 2001, PMID:11553629 — CPT1A H473A loss (compiled onto this CRAT His322) S5 — Kinetics: BRENDA EC 2.3.1.21 — no k_cat/K_m re-asserted on this page

› 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., palmitoyl-CoA, CoA, acylcarnitine, proton/nucleophile flight, product release), the pose is drawn schematically and labeled as such in the narration. 1S5O L-carnitine is an overlay, not this ternary.

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