M-phase Inducer Phosphatase 2 - 3D Mechanism Simulator

Loading structural data… (1QB0)

References & Databases

START HERE — how to read CDK-pTyr15 + H₂O → CDK-Tyr15 + Pi A single brake-off cartoon on the human CDC25B catalytic-domain frame that exists: 1QB0 (1.91 Å), chain A, with sulfate. That sulfate is a named occupancy, not phospho-Tyr and not Pi. The phospho-Tyr peptide is [schematic]. Dephospho-peptide, cysteinyl-P, Pi, and water are [schematic]. Cys473 is the HCX5R nucleophile on this mesh (plan Cys487 is Ile487 here). Gold H⁺ leaves water; blue is the Cys-SG nucleophile, not a hydride. Overlay peptide distances are not geomClaims. CDC25A/C are other genes. Dual-specificity teaching = Tyr15-P. Not a pure A-page (E~P covalent).
Crystal structures PDB 1QB0 — human CDC25B catalytic domain + sulfate, 1.91 Å (Reynolds 1999). Coordinates are public. 1CWR / 1CWS are small-molecule overlays — not this mesh. CDC25A/C structures are other genes.
Mechanism — Cys473 nucleophile, cysteinyl-P, water hydrolysis Reynolds et al., J. Mol. Biol. 1999, PMID:10543950 — CDC25B catalytic domain. UniProt P30305 HCX5R nucleophile maps to Cys473 on 1QB0 (Ile487 is not the nucleophile on this deposit). Arg479 orients the phosphate mimic. Product is free CDK-Tyr15 (brake off). Physiological acceptor teaching = CDK1/2 pTyr15 — analog, not this mesh. Source: Reynolds 1999 · UniProt P30305
0 — Setup: sulfate occupies the phosphate cleft 1QB0 holds CDC25B and sulfate. The sulfate is the crystal occupant — not phospho-Tyr and not Pi. Opaque, no autoplay. Chemistry below uses schematic pTyr peptide.Source: PDB 1QB0
① — CDK-pTyr15 analog presented A short CDK-pTyr15 analog docks as a named stand-in for CDK1/2 Tyr15-P — [schematic], not CDK1 and not a crystal peptide. Phosphate faces Cys473. Overlay peptide Å are not geomClaims. Dual-specificity teaching = Tyr15-P, not Thr14-P.Source: compiled CDC25 substrate identity · UniProt P30305
② — Cys473 attacks P → covalent E~P (hypothetical, lit.-based) Blue nucleophile rides from Cys473 SG to analog P. Phospho-peptide fades in place to schematic Tyr analog + covalent E~P. Overlay phospho-peptide Å are not geomClaims. Slow-motion on purpose. Not a pure A-page.Source: compiled CDC25 HCX5R · UniProt P30305
③ — Dephospho-Tyr15 leaves (hypothetical, lit.-based) Schematic Tyr analog departs. E~P stays on Cys473. Brake teaching = phosphate off the CDK.Source: EC 3.1.3.48 net accounting
④ — Water hydrolyses E~P → Pi (hypothetical, lit.-based) Gold H⁺ leaves water H2. Remaining OH⁻ attacks E~P. E~P fades to schematic Pi. Water is consumed. Overlay hydrolysis Å are not geomClaims.Source: compiled CDC25 hydrolysis · UniProt P30305
⑤ — Pi leaves — brake off [schematic] Pi departs. Product is free CDK-Tyr15. CDC25A/C are other genes. Sulfate was occupancy, not this chemistry.Source: EC 3.1.3.48 net accounting

How to read this page — a first-pass primer First pass: Setup (SO₄ seated, Cys473 ★) → ① pTyr analog docks → ② blue SG → P, peptide becomes Tyr analog + E~P → ③ Tyr analog leaves → ④ gold H⁺ then OH⁻ attacks E~P → Pi → ⑤ Pi leaves; brake off. Second pass: 3.11 / 3.30 / 2.86 / 3.05 Å are crystal facts on 1QB0; peptide, E~P, Pi, water, and H spheres are [schematic]. Third pass: open “Disagreements” for sulfate ≠ pTyr, Cys473 vs plan Cys487, CDC25A/C, and dual-specificity.
Chemistry primer — dual-specificity phosphatase, not PTP1B CDC25B transfers the CDK inhibitory phosphate to a cysteinyl-P, then water hydrolyses E~P. Gold = H⁺. Blue = Cys-SG nucleophile (not hydride). Product is free CDK-Tyr15 — brake off. This is not Wee1 adding Tyr15-P, and not PTP1B on a phosphotyrosine signaling protein.
Words used on screen — occupancy · analog · brake · CDC25A/C Occupancy — sulfate is the crystal ligand; never relabeled as pTyr or Pi. Analog — the pTyr peptide is a short model occupancy for CDK1/2 Tyr15-P. Brake off — removing CDK-Tyr15-P lets CDK fire. CDC25A / CDC25C — other genes. PDB numbering = UniProt P30305 catalytic domain; Cys473 is the nucleophile on 1QB0.

Legend & Fidelity

Mechanism fidelity — measured vs. inferred The measured layer: 1QB0 (1.91 Å) with sulfate; Cys473 SG ⋯ SO4 O2 = 3.11 Å; Cys473 SG ⋯ SO4 S = 3.30 Å; Arg479 NE ⋯ SO4 O3 = 2.86 Å; Arg479 NH2 ⋯ SO4 O2 = 3.05 Å. The inferred layer ([schematic]): pTyr peptide, dephospho-peptide, E~P, Pi, water, transferring H⁺/nucleophile spheres, product leave, and capture/hydrolysis split. Binding order is compiled staging, not a kinetic fit. The protein mesh is static. Overlay peptide contacts are not geomClaims. Cys473 is 1QB0 HCX5R, not plan Cys487.
Disagreements on record (a) Sulfate ≠ pTyr ≠ Pi. SO₄ is occupancy. (b) Peptide ≠ CDK1. pTyr analog is a model occupancy. (c) Numbering. UniProt P30305 ACT_SITE is Cys487; the 1QB0 mesh numbers the equivalent nucleophile Cys473 and its residue 487 is an Ile. (d) Capture vs hydrolysis split. Compiled CDC25 writes two chemical events; this page plays five beats. (e) CDC25A/C are other genes. (f) 1CWR / 1CWS are not this mesh. (g) No protein-domain swing. (h) Not a pure A-page — E~P is covalent.
Regulation — brake off · Wee1 · 14-3-3 · isoforms Brake off — CDC25 removes CDK-Tyr15-P so CDK can fire. Wee1 puts that phosphate on (other page). Nuclear/cytosol teaching isoform. CDC25A and CDC25C are other genes.Source: UniProt P30305 · Reynolds 1999 PMID:10543950
Kinetics scope (no measured timecourse on this page) One CDK-pTyr15 + H₂O → CDK-Tyr15 + Pi event is drawn, not a steady-state run. Compiled BRENDA values for EC 3.1.3.48 are not re-asserted here — no measured k_cat/K_m on this page [schematic]. Pair with a kinetics chapter.Source: BRENDA EC 3.1.3.48 — no k_cat/K_m re-asserted
Sequence Human CDC25B UniProt P30305 · NCBI Gene 994. Screen uses 1QB0 PDB-author numbering of the catalytic domain. Kinase-interacting N-terminus not on this mesh.
Simulation map — what you see is what is written Setup = 1QB0 SO₄ seated (opaque, no autoplay). ① pTyr analog moves in (schematic). ② slow-mo: blue nucleophile SG → P; peptide fades to Tyr analog + E~P. ③ Tyr analog leaves. ④ gold H⁺ then OH⁻ attacks E~P; E~P fades to Pi. ⑤ Pi leaves; brake off. Only these events move.
Sources — bibliography of this page S1 — PDB 1QB0: human CDC25B catalytic domain·SO₄, 1.91 Å — public coordinates; measured SG⋯O2 = 3.11 Å · SG⋯S = 3.30 Å · NE⋯O3 = 2.86 Å · NH2⋯O2 = 3.05 Å S2 — Reynolds et al., J. Mol. Biol. 1999, PMID:10543950 — catalytic domain of CDC25B S3 — Sequence: UniProt P30305 (human CDC25B) · NCBI Gene 994 S4 — Kinetics: BRENDA EC 3.1.3.48 — 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., pTyr peptide, dephospho-peptide, cysteinyl-P, Pi, H⁺ flight, product release), the pose is drawn schematically and labeled as such in the narration.

CDC25BONH⁺ (gold)nucleophile (blue)