Protein Phosphatase 2A Catalytic Subunit Alpha

Loading structural data… (2IE4)

References & Databases

START HERE — how to read protein-pSer + H₂O → protein-Ser + Pi A single mitotic-exit cartoon on the human PP2A catalytic frame that exists: 2IE4 (2.60 Å), chain C, with okadaic acid and dual Mn. That toxin is a named occupancy, not phospho-Ser and not Pi. Dual Mn stay. The phospho-Ser peptide is [schematic]. Dephospho-peptide, Pi, and water are [schematic]. His118 is the compiled PPP general acid (not a UniProt ACT_SITE). Gold H⁺ parks on His118; blue is the water-OH nucleophile, not a hydride. Overlay peptide distances are not geomClaims. Scaffold A is named occupancy, not animated. PPP2CB is another gene. 2IE3 microcystin is not this mesh. A-page (no covalent E~P).
Crystal structures PDB 2IE4 — human PP2A core enzyme + okadaic acid + Mn, 2.60 Å (Xing 2006). Coordinates are public. 2IE3 is the microcystin companion — not this mesh. PPP2CB structures are another gene. Regulatory B subunit is not on this deposit.
Mechanism — dual Mn activate water, His118 acid Xing et al., Cell 2006, PMID:17055435 — PP2A core enzyme bound to tumor-inducing toxins. UniProt P67775 has no ACT_SITE; His118 is the compiled PPP general acid. Dual Mn (Asp85, His241, His59, Asn117, His167, Asp57) stay. Product is free Ser/Thr (mitotic exit). Physiological substrate teaching = a mitotic phosphoprotein — analog, not this mesh. Source: Xing 2006 · UniProt P67775
0 — Setup: okadaic acid occupies the phosphate cleft 2IE4 holds PP2A-C, okadaic acid, and dual Mn. The toxin is the crystal occupant — not phospho-Ser and not Pi. Opaque, no autoplay. Chemistry below uses schematic pSer peptide.Source: PDB 2IE4
① — phospho-Ser analog presented A short phospho-Ser analog docks as a named stand-in for a mitotic phosphoprotein — [schematic], not a crystal peptide and not a named CDK site. Phosphate faces dual Mn. Overlay peptide Å are not geomClaims.Source: compiled PP2A substrate identity · UniProt P67775
② — dual Mn²⁺ deprotonate the bridging water (hypothetical, lit.-based) A schematic water glides in to the Mn₂ bridge (no sudden pop). The dual Mn²⁺ lower its pKₐ, so gold H⁺ is released to solvent and is taken up (no lingering parked ball). The remaining O–H1 is the bridging hydroxide nucleophile. His118 is the compiled general acid (it protonates the leaving Ser Oγ in ③), not the base. Dual Mn stay.Source: compiled PPP metallophosphatase · UniProt P67775
③ — OH⁻ attacks P; His118 protonates Ser Oγ (hypothetical, lit.-based) The OH⁻ itself (the water O) rides onto the analog P and becomes the new Pi oxygen — the moving ball is the nucleophile, not a separate marker. In the same beat the compiled general acid His118 ★ donates H⁺ to the leaving Ser Oγ, so the peptide departs as Ser–OH. Phospho-peptide fades in place to schematic Ser analog + Pi. Water is consumed. Overlay peptide Å are not geomClaims. Slow-motion on purpose. A-page.Source: compiled PPP hydrolysis · UniProt P67775
④ — Dephospho-Ser analog leaves (hypothetical, lit.-based) Schematic Ser analog departs. Dual Mn and Pi stay. Teaching = phosphate off a mitotic phosphoprotein.Source: EC 3.1.3.16 net accounting
⑤ — Pi leaves — mitotic exit [schematic] Pi departs. Dual Mn stay. Product is free protein-Ser. PPP2CB is another gene. Okadaic acid was occupancy, not this chemistry. Scaffold A never moved.Source: EC 3.1.3.16 net accounting

How to read this page — a first-pass primer First pass: Setup (OKA+MN seated, His118 ★) → ① pSer analog docks → ② the water glides in, the dual Mn release H⁺ (no parked ball) → ③ the OH⁻ itself rides onto P while His118 protonates the leaving Ser Oγ, peptide becomes Ser analog + Pi → ④ Ser analog leaves → ⑤ Pi leaves; mitotic exit. Second pass: 1.95 / 2.09 / 2.32 / 2.03 Å are crystal facts on 2IE4; peptide, Pi, water, and H spheres are [schematic]. Third pass: open “Disagreements” for okadaic acid ≠ pSer, His118 compiled, PPP2CB, and 2IE3.
Chemistry primer — metallophosphatase, not CDC25 PP2A-C transfers the phosphate to water at a dual-Mn center. Gold = H⁺. Blue = water-OH nucleophile (not hydride). Product is free protein-Ser — mitotic exit. This is not CDC25 removing CDK-Tyr15-P, and not Wee1 adding it. A-page: no covalent E~P.
Words used on screen — occupancy · analog · mitotic exit · PPP2CB Occupancy — okadaic acid is the crystal ligand; never relabeled as pSer or Pi. Analog — the pSer peptide is a short model occupancy for a mitotic phosphoprotein. Mitotic exit — removing mitotic phosphates lets the cell leave mitosis. PPP2CB — other gene. PDB numbering = UniProt P67775 catalytic chain C; scaffold A is offset +1000 on the tube.

Legend & Fidelity

Mechanism fidelity — measured vs. inferred The measured layer: 2IE4 (2.60 Å) with okadaic acid and dual Mn; Asp85 OD2 ⋯ MN2 = 1.95 Å; His241 ND1 ⋯ MN1 = 2.09 Å; His59 NE2 ⋯ MN2 = 2.32 Å; Asn117 OD1 ⋯ MN1 = 2.03 Å. The inferred layer ([schematic]): pSer peptide, dephospho-peptide, Pi, water, transferring H⁺/nucleophile spheres, product leave, and deprotonation/attack split. Binding order is compiled staging, not a kinetic fit. The protein mesh is static. Overlay peptide contacts are not geomClaims. His118 is compiled, not UniProt ACT_SITE.
Disagreements on record (a) Okadaic acid ≠ pSer ≠ Pi. OKA is occupancy. (b) Peptide ≠ a named CDK site. pSer analog is a model occupancy. (c) His118 is compiled. UniProt P67775 has no ACT_SITE. (d) Deprotonation vs attack split. Compiled PPP writes them as one event; this page plays two beats. (e) PPP2CB is another gene. (f) 2IE3 is the microcystin companion, not this mesh. (g) No protein-domain swing. Scaffold A does not morph. (h) Regulatory B is not on this deposit.
Regulation — mitotic exit · toxins · isoforms Mitotic exit — PP2A-C removes mitotic phosphates. Okadaic acid is a named toxin occupancy on this mesh, not a substrate. Scaffold A is required occupancy (named, not animated). PPP2CB is another gene. Regulatory B subunits are other proteins, not this mesh.Source: UniProt P67775 · Xing 2006 PMID:17055435
Kinetics scope (no measured timecourse on this page) One protein-pSer + H₂O → protein-Ser + Pi event is drawn, not a steady-state run. Compiled BRENDA values for EC 3.1.3.16 are not re-asserted here — no measured k_cat/K_m on this page [schematic]. Pair with a kinetics chapter.Source: BRENDA EC 3.1.3.16 — no k_cat/K_m re-asserted
Sequence Human PPP2CA UniProt P67775 · NCBI Gene 5515. Screen uses 2IE4 PDB-author numbering of the catalytic chain. Scaffold A is a named Cα trace (offset +1000). Regulatory B not on this mesh.
Simulation map — what you see is what is written Setup = 2IE4 OKA+MN seated (opaque, no autoplay). ① pSer analog moves in (schematic). ② the water glides in; the dual Mn release H⁺ (no parked ball) to give the bridging OH⁻. ③ slow-mo: the OH⁻ itself rides onto P (becoming the Pi oxygen) while the compiled general acid His118 donates H⁺ to the leaving Ser Oγ; peptide fades to Ser analog + Pi. ④ Ser analog leaves. ⑤ Pi leaves; mitotic exit. Only these events move.
Sources — bibliography of this page S1 — PDB 2IE4: human PP2A core·OKA·MN, 2.60 Å — public coordinates; measured OD2⋯MN2 = 1.95 Å · ND1⋯MN1 = 2.09 Å · NE2⋯MN2 = 2.32 Å · OD1⋯MN1 = 2.03 Å S2 — Xing et al., Cell 2006, PMID:17055435 — PP2A core enzyme bound to tumor-inducing toxins S3 — Sequence: UniProt P67775 (human PPP2CA) · NCBI Gene 5515 S4 — Kinetics: BRENDA EC 3.1.3.16 — 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., pSer peptide, dephospho-peptide, Pi, H⁺ flight, product release), the pose is drawn schematically and labeled as such in the narration.

PP2A-Cscaffold AONH⁺ (gold)nucleophile (blue)