UDP-glucose Pyrophosphorylase - 3D Mechanism Simulator

Loading structural data… (4R7P)

References & Databases

START HERE — how to read G1P + UTP → UDPG + PPi A nucleotidyl-transfer cartoon on the human UGP2 frame that actually exists: 4R7P (3.35 Å) isoform 1 with crystal UPG (UDP-glucose product analog). UTP, G1P, and PPi are [schematic] splits of that occupancy — not a ternary. Crystal Zn is crystallization (zinc acetate near Glu47), not physiological Mg (named). Lys396 is UniProt ACT_SITE; NZ⋯PA is far on this pose — named, not a contact. No covalent nucleotidyl-enzyme (A-page). White is phosphoryl / nucleotidyl transfer (P attack), not hydride. Measured Å are deposited 4R7P pairs only. Octamer assembly is not this chain-A cartoon.
Crystal structures PDB 4R7P — human UGP2 isoform 1 + UPG, 3.35 Å (Fuhring 2015). Coordinates are public. 3R2W / 3R3I are apo / truncated companions — no UDPG, not this mesh.
Mechanism — nucleotidyl transfer UniProt Q16851 EC 2.7.7.9: G1P + UTP + H⁺ → UDPG + PPi. Fuhring et al., Sci Rep 2015, PMID:25860585 — octameric human UGP + UDP-Glc. This page is chain A. Source: UniProt Q16851 · Fuhring 2015
0 — Setup: Zn present, pocket shown empty 4R7P holds UPG and crystallization Zn. The pocket is shown empty so ordered binding can start. Zn stays as a named occupant (physiological metal is Mg). Opaque, run:null (no autoplay). Lys396 is ACT_SITE, not a deposited nucleophile contact.Source: PDB 4R7P (3.35 Å)
① — UTP binds Schematic UTP docks as uridine + PA of crystal UPG plus a teaching β/γ-phosphate (PB/PC) — [schematic], not a deposited UTP. UPG PB is the G1P phosphate in the product, not UTP β. Crystal UPG is the product analog, not this ligand.Source: 4R7P UPG occupancy split
② — Glucose 1-phosphate binds Schematic G1P docks as the glucose half of crystal UPG plus a teaching phosphate — not a 4R7P ternary. Glu47 OE2 ⋯ Zn = 2.23 Å (crystallization metal). G1P here is from PGM1.Source: 4R7P Zn-614 / Glu47
③ — G1P-O attacks UTP α-P → UDPG + PPi (hypothetical, lit.-based) White nucleophile rides from G1P phosphate O to schematic UTP PA. UTP + G1P fade in place to crystal UPG and schematic PPi. No covalent nucleotidyl-enzyme. Slow-motion on purpose.Source: compiled UGP nucleotidyl transfer · UniProt Q16851
④ — Crystal UDP-glucose is the product analog Crystal UPG is the deposited product analog. His223 NE2 ⋯ UPG PB = 4.14 Å. Asp253 OD2 ⋯ UPG PA = 4.45 Å. Lys396 NZ⋯PA is ~10 Å on this pose — named ACT_SITE, not a geomClaim.Source: 4R7P UPG pose
⑤ — UDPG and PPi leave — GYG1 next [schematic PPi] UDPG and PPi depart opposite ways. Zn stays. UDPG is the donor for GYG1 (primer) and GYS1 (elongation). This page does not glycosylate Tyr195.Source: glycogen-synthesis bookkeeping

How to read this page — a first-pass primer First pass: Setup (Zn present, pocket empty, Lys396 ★) → ① schematic UTP docks → ② schematic G1P docks → ③ white G1P-O → UTP PA, fade to crystal UPG + PPi → ④ UPG named as product analog → ⑤ UDPG and PPi leave opposite ways; Zn stays. Second pass: 4.14 Å / 4.45 Å / 2.23 Å are crystal facts on 4R7P; UTP, G1P, and PPi are [schematic]. Third pass: open “Disagreements” for Zn vs Mg, Lys396 distance, octamer vs chain A, and product analog vs ternary.
Chemistry primer — nucleotidyl transfer UGP2 activates G1P with UTP. The sugar phosphate oxygen attacks UTP α-P; PPi leaves. Product is UDP-glucose, the universal glucose donor for glycogenin and glycogen synthase. Gold is unused on this page (net H⁺ is in the EC equation, not drawn as a sphere). White = phosphoryl / nucleotidyl transfer (P attack), not hydride. This is not PGM1 (G1P ⇌ G6P) and not GYS1 (glycogen elongation).
Words used on screen — UPG analog · crystallization Zn · octamer UPG — deposited UDP-glucose product analog on 4R7P, not a Michaelis ternary. Crystallization Zn — zinc acetate occupant near Glu47; physiological metal is Mg. Octamer — biological assembly is D4 octamer; this cartoon is chain A.

Legend & Fidelity

Mechanism fidelity — measured vs. inferred The measured layer: 4R7P (3.35 Å) with UPG and Zn; His223 NE2 ⋯ UPG PB = 4.14 Å; Asp253 OD2 ⋯ UPG PA = 4.45 Å; Glu47 OE2 ⋯ Zn = 2.23 Å. The inferred layer ([schematic]): UTP, G1P, PPi, transferring nucleophile sphere, product leave. Binding order is compiled staging, not a kinetic fit. The protein mesh is static. Schematic G1P⋯UTP and Lys396 NZ⋯PA (~10 Å) are not geomClaims.
Disagreements on record (a) UPG ≠ UTP ≠ G1P. Crystal UDP-glucose is the product analog. (b) Zn ≠ physiological metal. UniProt / literature list Mg; 4R7P holds crystallization Zn. (c) Lys396 is ACT_SITE, not a contact on this pose. NZ⋯PA ~10 Å — named, not claimed. (d) Octamer vs chain A. Fuhring 2015 is an octameric enzyme; this page is one chain. (e) No covalent nucleotidyl-enzyme (A-page). (f) 3R2W apo is not this sugar story.
Regulation — isoforms · octamer This mesh is UGP2 isoform 1. The biological unit is an octamer (Fuhring 2015). Cytosolic nucleotidyltransferase feeding UDPG into glycogenin / glycogen synthase. No GSD allele is simulated.Source: UniProt Q16851 · Fuhring 2015 PMID:25860585
Kinetics scope (no measured timecourse on this page) One G1P + UTP → UDPG + PPi event is drawn, not a steady-state run. Compiled BRENDA values for EC 2.7.7.9 are not re-asserted here — no measured k_cat/K_m on this page [schematic]. Pair with a kinetics chapter.Source: BRENDA EC 2.7.7.9 — no k_cat/K_m re-asserted
Sequence Human UGP2 UniProt Q16851 · NCBI Gene 7360. Screen uses 4R7P PDB-author numbering (Lys396, His223, Asp253, Glu47). Chain A. Cα 24–508.
Simulation map — what you see is what is written Setup = 4R7P pocket empty, Zn visible (opaque, no autoplay). ① schematic UTP moves in. ② schematic G1P moves in. ③ slow-mo: white nucleophile G1P-O → UTP PA; UTP+G1P fade to crystal UPG + PPi. ④ UPG named as product analog. ⑤ UDPG and PPi leave opposite ways; Zn stays. Only these events move.
Sources — bibliography of this page S1 — PDB 4R7P: human UGP2 isoform 1, 3.35 Å, UPG + Zn — public coordinates; measured NE2⋯PB = 4.14 Å · OD2⋯PA = 4.45 Å S2 — Fuhring et al., Sci Rep 2015, PMID:25860585 — octameric human UGP + UDP-Glc S3 — Sequence: UniProt Q16851 (human UGP2) · NCBI Gene 7360 S4 — Kinetics: BRENDA EC 2.7.7.9 — 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., UTP, G1P, PPi, nucleophile flight, product release), the pose is drawn schematically and labeled as such in the narration.

N-domainC-domainONphosphoryl (white)