Argininosuccinate lyase - 3D Mechanism Simulator

Loading structural data… (1K62)

References & Databases

START HERE — how to read argininosuccinate → fumarate + L-arginine A β-elimination cartoon on the human ASL frame that actually exists: 1K62 (2.65 Å) chain A, the frequent-complementing Q286R mutant, with no substrate ligand. Occupancy is empty (HOH only), not argininosuccinate, not arginine, not fumarate — never label the empty pocket as bound AS. His160 ★ is this PDB = UniProt ACT_SITE acceptor. Residue 281 is SER — UniProt ACT_SITE donor (named, not starred); do not pin His281. Residue 286 is ARG (Q286R); the side chain is missing (backbone only) — do not pin WT Gln286. Argininosuccinate / arginine / fumarate are [schematic] near His160. 1DCN duck δ2-crystallin H162N + AS1 is a named overlay, not this mesh, not geomClaims. Missing 1–14 is not this mesh (Cα 15–464). Homotetramer named; teaching is chain A. Gold is compiled C2–H taken by His160, not a net-EC proton. No blue nitrogen nucleophile. No white phosphoryl. ARG1 next. Measured distances are deposited 1K62-A protein pairs only.
Crystal structures PDB 1K62 — human ASL Q286R, 2.65 Å, no substrate (Sampaleanu 2001). Coordinates are public. Occupancy is empty (HOH only). PDB 1DCN is duck δ2-crystallin H162N + AS1 — named overlay, not this mesh. Human ASL UniProt P04424.
Mechanism — His160/Ser281 ACT_SITE pair; empty occupancy; Q286R UniProt P04424 EC 4.3.2.1: 2-(Nω-L-arginino)succinate = fumarate + L-arginine. This page teaches β-elimination (urea cycle, cytosol). On this mesh the ACT_SITE histidine is His160 (proton acceptor). Residue 281 is SER — the paired UniProt ACT_SITE proton donor (named, not starred), not His. Residue 286 is ARG (Q286R). ARG1 is next. Source: UniProt P04424 · Sampaleanu 2001
0 — Setup: empty ASL pocket 1K62 occupancy is empty (HOH only), not argininosuccinate. The pocket is shown empty so binding can start. Opaque, run:null (no autoplay). His160 ★ is the ACT_SITE acceptor. Q286R spoken — residue 286 is ARG, side chain missing. Residue 281 is SER — the ACT_SITE donor. Missing 1–14 is not this mesh (Cα 15–464). 1DCN duck AS1 is a named overlay. Homotetramer named; teaching is chain A.Source: PDB 1K62 (2.65 Å)
① — Argininosuccinate binds [schematic] Argininosuccinate docks near His160 NE2 — not deposited. Occupancy is empty; never label the empty pocket as bound AS. His160 ND1 ⋯ Thr159 O = 3.29 Å and His160 ND1 ⋯ Thr159 OG1 = 3.38 Å are deposited 1K62 protein pairs. 1DCN duck AS1 distances are not geomClaims.Source: PDB 1K62 empty fold + schematic AS
② — His160 takes C2-H (hypothetical, lit.-based) Gold ball + gold arrow: His160 ★ takes schematic argininosuccinate C2–H. Gold is the compiled C2 proton, not a net-EC H⁺. Occupancy is empty. Residue 281 is SER — UniProt ACT_SITE donor (named, not starred); do not pin His281. Slow-motion on purpose. No blue nitrogen nucleophile. No white phosphoryl.Source: compiled C2–H · Sampaleanu 2001 · UniProt P04424 His160
③ — β-elimination (hypothetical, lit.-based) After C2–H abstraction, the schematic argininosuccinate C3–NE linkage heats, thins and snaps at T.react while schematic L-arginine and schematic fumarate emerge in place through the swap beat — no positional drift, so step ④ starts exactly where ③ ends. His160 ★ and Ser281 pin only briefly (~1 s) as the ACT_SITE acceptor/donor halves, then clear. Occupancy is empty; never label the empty pocket as bound AS. 1DCN duck AS1 is not this mesh. Q286R spoken. Slow-motion on purpose. No arrows on this step.Source: compiled β-elimination · Sampaleanu 2001 · UniProt P04424
④ — Opposite leave — ARG1 next Schematic L-arginine departs one way; schematic fumarate departs the other. Arginine is the substrate of ARG1 (next). This page does not hydrolyse arginine. 1K62 occupancy is empty, not argininosuccinate. Q286R spoken. Residue 281 is SER — UniProt ACT_SITE donor (named, not starred). Net EC H⁺ is not a gold sphere. His160 ★ is ACT_SITE.Source: urea-cycle bookkeeping · EC 4.3.2.1

How to read this page — a first-pass primer First pass: Setup (empty pocket, His160 ★ acceptor, Q286R, Ser281 donor) → ① schematic argininosuccinate docks → ② gold C2–H to His160 NE2 → ③ C3–NE opens at T.react, then fade to arginine + fumarate → ④ opposite leave; ARG1 next. Second pass: 3.29 / 3.38 Å are crystal facts on 1K62 protein pairs; AS / Arg / fumarate are [schematic]; occupancy is empty. Third pass: open “Disagreements” for Q286R, Ser281, 1DCN duck overlay, and compiled C2–H.
Chemistry primer — argininosuccinate lyase ASL eliminates fumarate from argininosuccinate, releasing L-arginine. His160 (acceptor) + Ser281 (donor) are the UniProt ACT_SITE pair. Gold is compiled C2–H, not a net-EC proton. No blue nitrogen nucleophile. No white phosphoryl. This is cytosolic, not mitochondrial. Not a hydrolase.
Words used on screen — empty occupancy · Q286R · Ser281 · His160 ★ Empty occupancy — 1K62 holds HOH only, not AS. Q286R — residue 286 is ARG; side chain missing. Ser281 — SER, not His; UniProt ACT_SITE proton donor paired with His160 (named, not starred). His160 ★ — ACT_SITE proton acceptor on this PDB = UniProt.

Legend & Fidelity

Mechanism fidelity — measured vs. inferred The measured layer: 1K62 (2.65 Å) human ASL Q286R chain A empty; His160 ND1 ⋯ Thr159 O = 3.29 Å; His160 ND1 ⋯ Thr159 OG1 = 3.38 Å. The inferred layer ([schematic]): argininosuccinate / arginine / fumarate near His160, transferring C2–H sphere. Binding order is compiled staging, not a kinetic fit. The protein mesh is static. Overlay / schematic / 1DCN AS1 distances are not geomClaims.
Disagreements on record (a) Occupancy vs substrates. 1K62 is empty, not argininosuccinate. (b) Q286R. Residue 286 is ARG, not WT Gln; side chain missing. (c) Residue 281 is SER, not His — and it is the UniProt ACT_SITE proton donor (His160 is the acceptor); do not mislabel it His and do not teach it as non-catalytic. (d) His160 ★ is the ACT_SITE acceptor; compiled C2–H is not deposited. (e) 1DCN is duck δ2-crystallin H162N + AS1 — named overlay, not this mesh. (f) Partner-chain B contacts are named, not claims. (g) Missing 1–14 is not this mesh (Cα 15–464). (h) Homotetramer assembly is not this cartoon. (i) Gold C2–H is not a net-EC proton. (j) Not a hydrolase. (k) Overlay/schematic distances are not claims.
Regulation — cytosol · homotetramer · next ARG1 This elimination is cytosolic ASL only. Arginine is the substrate of ARG1 — not this mesh. Homotetramer is named, not animated. Q286R is the frequent complementing allele on this mesh.Source: UniProt P04424 · PDB 1K62 · Sampaleanu 2001
Kinetics scope (no measured timecourse on this page) One argininosuccinate → fumarate + L-arginine event is drawn, not a steady-state run. Compiled BRENDA values for EC 4.3.2.1 are not re-asserted here — no measured k_cat/K_m on this page [schematic]. Pair with a kinetics chapter.Source: BRENDA EC 4.3.2.1 — no k_cat/K_m re-asserted
Sequence Human ASL UniProt P04424 · NCBI Gene 435. This screen uses 1K62 numbering (His160 = UniProt His160; residue 281 = Ser; residue 286 = Arg). Chain A. Cα 15–464. Missing 1–14 is not this mesh.
Simulation map — what you see is what is written Setup = 1K62 pocket empty (opaque, no autoplay). ① schematic argininosuccinate moves in. ② slow-mo: gold C2–H → His160 NE2. ③ slow-mo: C3–NE opens; fade to arginine + fumarate. ④ arginine and fumarate leave opposite ways. Only these events move.
Sources — bibliography of this page S1 — PDB 1K62: human ASL Q286R empty, 2.65 Å — public coordinates; measured His160 ND1⋯Thr159 O = 3.29 Å · His160 ND1⋯Thr159 OG1 = 3.38 Å S2 — Sampaleanu et al., J. Mol. Biol. 2001, PMID:11747432 — human ASL Q286R S3 — Sequence: UniProt P04424 · NCBI Gene 435 S4 — Kinetics: BRENDA EC 4.3.2.1 — no k_cat/K_m re-asserted on this page S5 — PDB 1DCN duck δ2-crystallin H162N + AS1 — named overlay, not this mesh (PMID:10029536)

› Backbones are taken directly from the listed PDB entries, superposed into one common frame. Where no crystalline state exists for a step (e.g., argininosuccinate, arginine, fumarate, C2–H flight, product leave), the pose is drawn schematically and labeled as such in the narration. Occupancy is empty, not argininosuccinate. Overlay / schematic / 1DCN AS1 distances are not geomClaims. 1DCN is named, not extracted.

N-domainC-domainONC2–H (gold)