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START HERE — how to read L-arginine + H₂O → urea + L-ornithine
A dimanganese hydrolase cartoon on the human ARG1 frame that actually exists: 3GMZ (1.43 Å) chain A with crystal L-ornithine + Mn×2. Occupancy is the hydrolysis product, not arginine, not urea — never label crystal ORN as arginine. TITLE = complex with L-ornithine. His141 ★ is compiled proton shuttle (UniProt annotates ornithine binding, not ACT_SITE). Mn ligands His101·His126·Asp124·Asp128·Asp232·Asp234 stay. HOH A527 bridges both Mn — named occupancy, not starred, not the schematic nucleophile. Arginine / urea / reactant water are [schematic]. 2AEB / 1WVA / 3GN0 are inhibitors, not this mesh. ARG2 is another gene. Missing 1–4 is not this mesh (Cα 5–319). Homotrimer named; teaching is chain A. Gold is compiled water-H taken by His141, not a net-EC proton. Blue is OH⁻ lone pair onto Arg CZ, not hydride. Water is consumed into urea. ORNT1 named, not a page. Measured distances are deposited 3GMZ-A occupancy pairs only — not arginine claims.
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Crystal structures
PDB 3GMZ — human ARG1 + L-ornithine, 1.43 Å (Ilies / Christianson 2011). Coordinates are public. Occupancy is product ornithine + Mn×2. PDB 2AEB ABH / 1WVA S2C / 3GN0 DMO are inhibitors — rejected, not this mesh. Human ARG1 UniProt P05089.
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Mechanism — His141 compiled; ORN is product; Mn stays
UniProt P05089 EC 3.5.3.1: L-arginine + H₂O = urea + L-ornithine. This page teaches the urea-cycle hydrolase (cytosol). On this mesh His141 is compiled (UniProt = ornithine binding, not ACT_SITE). HOH527 is not starred. ARG2 is another gene. ORNT1 return of ornithine is named, not a page. Source: UniProt P05089 · Ilies 2011
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0 — Setup: product ORN occupancy
3GMZ occupancy is product L-ornithine + Mn×2, not arginine. Mn stays visible. HOH A527 named, not starred. His141 ★ compiled. Missing 1–4 is not this mesh (Cα 5–319). Homotrimer named; teaching is chain A. ARG2 other gene. 2AEB / 1WVA / 3GN0 rejected. Opaque, run:null (no autoplay).Source: PDB 3GMZ (1.43 Å)
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① — Arginine binds
[schematic] L-arginine docks as the crystal ornithine chain plus a teaching guanidinium — never label crystal ORN as arginine. His101 ND1 ⋯ MN2 = 2.28 Å is deposited 3GMZ Mn occupancy, not an arginine claim. Mn stays.Source: PDB 3GMZ product occupancy + schematic ARG
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② — Catalytic water binds
[schematic] Reactant water docks toward His141 / Arg CZ — not HOH A527. HOH527 is the Mn-bridging water on the product frame; named occupancy, not extracted as nucleophile, not starred. His126 ND1 ⋯ MN1 = 2.40 Å is deposited Mn occupancy, not an arginine claim. This water is consumed into urea.Source: compiled hydrolase water · 3GMZ Mn cluster
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③ — His141 takes water-H
(hypothetical, lit.-based) Gold ball + thin gold shaft, no head: His141 ★ takes schematic water H2. Gold is the compiled water proton, not a net-EC H⁺. Removing H2 leaves OH⁻. Do not star HOH527. Occupancy is product ornithine, not arginine. His141 label clears ~1 s in so it never covers the transfer. Slow-motion on purpose. No white phosphoryl.Source: compiled His141 shuttle · Ilies 2011 · UniProt P05089
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④ — Hydrolysis — urea + ornithine
(hypothetical, lit.-based) Red O ball + gray H ball (the schematic water O-H pair itself, no arrow at all): OH⁻ (lone pair, not hydride) attacks schematic arginine CZ. Arginine cross-fades to schematic urea + crystal L-ornithine (the 3GMZ product). Water is consumed. Never label crystal ORN as arginine. His141 NE2 ⋯ ORN NE = 3.36 Å is deposited product occupancy, not an arginine claim. Slow-motion on purpose. Mn stays.Source: compiled hydrolysis · 3GMZ ORN product · Ilies 2011
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⑤ — Opposite leave — cycle complete
Schematic urea departs one way; crystal L-ornithine (product, not arginine) departs the other. Mn stays. Water was consumed into urea. Ornithine returns via ORNT1 — named, not a page. ARG2 is another gene. Net EC H⁺ is not a gold sphere. His141 ★ is compiled.Source: urea-cycle bookkeeping · EC 3.5.3.1
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How to read this page — a first-pass primer
First pass: Setup (product ORN, Mn stays, His141 ★ compiled, HOH527 named not starred) → ① schematic arginine docks → ② schematic water docks → ③ gold water-H to His141 NE2 → ④ blue OH⁻ to CZ, fade to urea + crystal ORN → ⑤ opposite leave; cycle complete. Second pass: 2.28 / 2.40 / 3.36 Å are crystal facts on 3GMZ occupancy (Mn cluster + product His141⋯ORN); arginine / urea / water are [schematic]; occupancy is product ornithine. Third pass: open “Disagreements” for ORN≠arginine, HOH527 not nucleophile, His141 compiled, ARG2, inhibitors.
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Chemistry primer — arginase-1
ARG1 hydrolyses L-arginine to urea + L-ornithine on a dimanganese cluster. His141 is compiled proton shuttle. Gold is compiled water-H, not a net-EC proton. Blue is OH⁻ nucleophile onto CZ, not hydride. Water is consumed into urea. This is cytosolic liver ARG1, not ARG2. Not a lyase.
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Words used on screen — product ORN · HOH527 · His141 ★ · Mn stays
Product ORN — 3GMZ holds L-ornithine, not arginine. HOH527 — Mn-bridge occupancy; not starred; not the schematic nucleophile. His141 ★ — compiled proton shuttle (UniProt = ornithine binding). Mn stays — two Mn per subunit, leaves:false.
Legend & Fidelity
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Mechanism fidelity — measured vs. inferred
The measured layer: 3GMZ (1.43 Å) human ARG1 chain A + ORN + MN×2; His101 ND1 ⋯ MN2 = 2.28 Å; His126 ND1 ⋯ MN1 = 2.40 Å; Asp124 OD2 ⋯ MN2 = 2.12 Å; Asp232 OD2 ⋯ MN1 = 2.26 Å; His141 NE2 ⋯ ORN NE = 3.36 Å. The inferred layer ([schematic]): arginine / urea / reactant water, transferring H⁺ and OH⁻ spheres. Binding order is compiled staging, not a kinetic fit. The protein mesh is static. Overlay / schematic distances are not geomClaims. Occupancy distances are not arginine claims.
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Disagreements on record
(a) Occupancy vs substrate. 3GMZ is product ornithine, not arginine. (b) TITLE = complex with L-ornithine — do not copy occupancy as arginine. (c) His141 ★ is compiled; UniProt = ornithine binding, not ACT_SITE. (d) HOH527 is Mn-bridge occupancy — not starred, not the nucleophile; His141 is not H-bonded to it on this mesh. (e) Bridging hydroxide as the true nucleophile is compiled (Christianson); this page teaches His141 shuttle + OH⁻ onto CZ as proposal. (f) 2AEB / 1WVA / 3GN0 are inhibitors, not this mesh. (g) ARG2 is another gene. (h) Missing 1–4 is not this mesh (Cα 5–319). (i) Homotrimer assembly is not this cartoon. (j) Gold water-H is not a net-EC proton. (k) Blue is OH⁻, not hydride. (l) Overlay/schematic distances are not claims. (m) Occupancy distances are not arginine claims. (n) ORNT1 is named, not a page.
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Regulation — cytosol · liver ARG1 · not ARG2 · ORNT1 named
This hydrolysis is cytosolic liver ARG1 only. ARG2 is extrahepatic — other gene. Ornithine returns to the matrix via ORNT1 — named, not a sixth page. Homotrimer is named, not animated. Mn stays.Source: UniProt P05089 · PDB 3GMZ · Ilies 2011
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Kinetics scope (no measured timecourse on this page)
One L-arginine + H₂O → urea + L-ornithine event is drawn, not a steady-state run. Compiled BRENDA values for EC 3.5.3.1 are not re-asserted here — no measured kcat/Km on this page [schematic]. Pair with a kinetics chapter.Source: BRENDA EC 3.5.3.1 — no kcat/Km re-asserted
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Sequence
Human ARG1 UniProt P05089 · NCBI Gene 383. This screen uses 3GMZ numbering (His141 = UniProt His141). Chain A. Cα 5–319. Missing 1–4 is not this mesh.
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Simulation map — what you see is what is written
Setup = 3GMZ Mn visible, product ORN hidden until hydrolysis (opaque, no autoplay). ① schematic arginine moves in. ② schematic water moves in. ③ slow-mo: gold water-H → His141 NE2. ④ slow-mo: blue OH⁻ → CZ, fade to urea + crystal ORN. ⑤ urea and ornithine leave opposite ways; Mn stays. Only these events move.
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Sources — bibliography of this page
S1 — PDB 3GMZ: human ARG1 + L-ornithine, 1.43 Å — public coordinates; measured His101 ND1⋯MN2 = 2.28 Å · His126 ND1⋯MN1 = 2.40 Å · Asp124 OD2⋯MN2 = 2.12 Å · Asp232 OD2⋯MN1 = 2.26 Å · His141 NE2⋯ORN NE = 3.36 Å
S2 — Ilies et al., J. Med. Chem. 2011, PMID:21728378 — human ARG1 + ornithine
S3 — Sequence: UniProt P05089 · NCBI Gene 383
S4 — Kinetics: BRENDA EC 3.5.3.1 — no kcat/Km re-asserted on this page
› Backbones and ORN / Mn poses are taken directly from the listed PDB entries,
superposed into one common frame. Where no crystalline state exists for a step
(e.g., arginine, urea, reactant water, H⁺ / OH⁻ flight, product leave), the pose is drawn
schematically and labeled as such in the narration. Occupancy is product ornithine, not arginine. Occupancy distances are not arginine claims. Overlay / schematic distances are not geomClaims. HOH527 is named, not extracted.