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Structure
Aleshin AE et al. Structure 1998;6:39–50 — HKI·glucose·G6P (PDB 1HKB) PMID:9493266; the viewer scaffold 4FOI (HK1 D413N + Glc-1,6BP) has no standalone PMID.
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ATP complex
Rosano C et al. Structure 1999;7:1427–37 — AMP-PNP·Mg (PDB 1QHA) PMID:10574795
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① Glucose binding (induced fit)
Ordered mechanism — glucose binds first and closes the two-domain cleft over it. Bound-glucose pose from HKI·glucose·G6P 1HKB (Aleshin AE et al., Structure 1998, PMID:9493266).
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② Mg·ATP docks opposite O6
[schematic] Gamma-P of ATP positioned ~3.4 Å behind O6 on the backside-attack line (pose from the AMP-PNP·Mg complex 1QHA, re-aligned). Mg²⁺ chelates the β/γ phosphates.
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③ Asp657 deprotonates the C6-OH (HT)
[schematic · hypothetical, lit.-based] Asp657 deprotonates the C6-OH (general-base proposal, M-CSA Entry 696); the alkoxide attacks Pγ in-line through a trigonal-bipyramidal transition state; configuration inverts.
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④ In-line S_N2 transfer (inversion)
[schematic] direct in-line phosphoryl transfer (no dissociative/free-metaphosphate branch). Ser603 · Arg539 · Mg²⁺ stabilize the TS (M-CSA Entry 696).
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⑤ Products leave — G6P + ADP + H⁺
G6P dissociates in its crystallographic pose; ADP follows; the H⁺ product regenerates Asp657 (M-CSA step 2). Glucose / G6P pose from 1HKB.
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Sequence
DNA/gene NCBI Gene 3098 · protein UniProt P19367
Legend & Fidelity
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Mechanism fidelity — the Asp657 "general base" is a proposal, not a direct measurement
A transition state can never be observed directly, so every arrow here is a mechanism inferred from crystallography and kinetics. M-CSA Entry 696 records the 6-OH ⋯ γ-P ≈ 3 Å in-line geometry with Asp657 abstracting the C6-OH proton, but it also notes a recent HK crystal structure whose data suggest the pKa of Asp657 is too low to abstract that proton — the proton may instead transfer later, on phosphate-bond formation.
· HT (③): we animate the classical general-base proposal and label it "(hypothetical, lit.-based)"; a later-step H⁺ transfer would keep the same in-line associative Sₙ2 chemistry and inversion.
· GT (④): in-line Sₙ2, associative — no dissociative / free-metaphosphate (Sₙ1) branch is proposed for HK1.
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Arrow & label conventions
Gold arrow = proton (H⁺) path; the moving gold ball is the H⁺ itself (schematic sphere, Rule 23). Blue arrow = attacking nucleophile (here O6⁻ → Pγ). Dashed lines track the γ-PO₃ flight: red dashed = the O3B–Pγ bond breaking (from the β-phosphate); gold dashed = the new O6–Pγ bond forming. The flying γ-PO₃ lands on the G6P phosphate of the product (continuity). Other H atoms are not drawn. Å labels = reaction coordinate. Colors follow the shared engine legend.
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Why is the Mg·ATP pose labeled "[schematic]"?
The AMP-PNP·Mg copy deposited in 1QHA binds a non-catalytic surface site on the N-terminal domain — not the catalytic cleft. The adenosine + Mg²⁺ are real 1QHA coordinates; the γ-PO₃ is rotated so Pγ faces O6 at ≈ 3.4 Å on the backside line — a Michaelis complex no HK1 crystal has yet captured. Glucose, G6P, Asp657 and Ser603 are real 1HKB geometry.
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Static protein, reconstructed motion
The protein mesh is static; the glucose-induced two-domain closure is conveyed by a label and the substrate's seating. Animations interpolate between real crystallographic states, and any reconstruction is "literature-based", not measured.
› 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., Michaelis geometry), the pose is drawn schematically using PubChem 3D
geometries and is labeled as such in the narration.
Residue numbers follow UniProt P19367 (HK1) and match the structure papers.