Cyclin-Dependent Kinase 2 - 3D Mechanism Simulator

Loading structural data… (1QMZ)

References & Databases

START HERE — how to read ATP + protein-Ser/Thr → ADP + protein-Ser/Thr-P A single kinase cartoon on the human CDK2·cyclin A pocket. Real crystal: 1QMZ (2.20 Å), chain A, with cyclin A chain B, ATP, Mg, phospho-Thr160 (TPO160), and a short HHASPRK peptide. That peptide is a model substrate analog [schematic], not Rb and not p27. Phospho-peptide and ADP are [schematic] on this frame. Asp127 is the UniProt proton acceptor. Gold H⁺ parks on Asp127; blue is the Ser-OH nucleophile, not a hydride. Cyclin A is required occupancy, not a swing. TPO160 is CAK activation, named, not the nucleophile. Schematic phospho-peptide distances are not geomClaims. CDK1 / CDK4 / CDK6 are other genes. 1FIN has no peptide — not this mesh.
Crystal structures PDB 1QMZ — human CDK2·cyclin A·ATP·Mg·peptide, 2.20 Å (Brown 1999). Coordinates are public. 1FIN is the no-peptide companion — not this mesh. 1B38 / 1HCK are monomeric CDK2 (inactive story = Overview). 1JST is phospho-CDK2·cyclin A without peptide. Drug soaks are not this page.
Mechanism — Asp127 base, in-line γ-PO₃ onto Ser/Thr-OH Brown et al., Nat Cell Biol 1999, PMID:10559988 — CDK2·cyclin A with ATP and a model peptide. UniProt P24941 ACT_SITE Asp127 is the proton acceptor; Lys33 orients ATP; Asp145 (DFG) holds Mg. No covalent phospho-enzyme. Product is protein-Ser/Thr-P, not a free sugar phosphate. Source: Brown 1999 · UniProt P24941
0 — Setup: cyclin A + TPO160 stay, peptide cleft shown empty 1QMZ holds CDK2, cyclin A, TPO160, ATP, Mg, and the peptide. The peptide cleft is shown empty so ordered binding can start. Cyclin A stays visible as required occupancy. TPO160 stays as activation, not a nucleophile. Opaque, no autoplay. Crystal peptide is a model analog, not Rb.Source: PDB 1QMZ
① — Substrate peptide presented (HHASPRK analog) Crystal HHASPRK docks as a named analog of a protein-Ser/Thr substrate — [schematic], not Rb, not histone, not p27. HHASPRK Ser OG (PDB residue 5, sequence position 4) faces ATP γ-P. Asp127 OD2 ⋯ PEP OG = 2.69 Å on this deposit.Source: 1QMZ peptide pose
② — Mg·ATP docks Crystal ATP and Mg dock. PEP OG ⋯ ATP PG = 3.68 Å; Lys33 NZ ⋯ ATP O1A = 3.00 Å; Asp145 OD2 ⋯ MG = 1.91 Å on this deposit. Overlay ADP distances are not geomClaims.Source: 1QMZ ATP + MG pose
③ — Asp127 deprotonates the Ser/Thr-OH (hypothetical, lit.-based) A gold H⁺ sphere rides a gold arrow from peptide OG to Asp127 OD2 and parks. Compiled kinase writes this proton transfer with the γ-PO₃ transfer; this page splits them.Source: UniProt P24941 ACT_SITE Asp127 · 1QMZ 2.69 Å
④ — In-line γ-PO₃ transfer → phospho-peptide (hypothetical, lit.-based) Blue nucleophile rides from peptide OG to ATP PG. Peptide + ATP fade in place to schematic phospho-peptide and schematic ADP. Parked gold H⁺ stays on Asp127. Overlay phospho-peptide Å are not geomClaims. Slow-motion on purpose. No covalent phospho-enzyme.Source: compiled CDK kinase · UniProt P24941
⑤ — Products leave — cyclin A stays [schematic] Phospho-peptide and ADP·Mg depart in opposite directions. Parked gold H⁺ leaves toward solvent. Cyclin A stays. TPO160 stays as activation. CDK7 phosphorylates this T-loop on another page.Source: EC 2.7.11.22 net accounting

How to read this page — a first-pass primer First pass: Setup (cyclin A + TPO160 present, peptide cleft empty, Asp127 ★) → ① peptide analog docks → ② ATP+Mg dock → ③ gold H⁺ OG → Asp127 (parks) → ④ blue nucleophile OG → PG, peptide+ATP become phospho-peptide+ADP → ⑤ products leave; cyclin A stays. Second pass: 2.69 / 3.68 / 3.00 / 1.91 Å are crystal facts on 1QMZ; phospho-peptide, ADP, and the H spheres are [schematic]. Third pass: open “Disagreements” for analog vs Rb/p27, 1FIN, CDK1/4/6, and concerted vs split.
Chemistry primer — protein kinase, not hexokinase CDK2 transfers ATP γ-phosphate onto a protein Ser/Thr in an SPXK/TPXK motif. Asp127 deprotonates the hydroxyl; the oxygen attacks γ-P in line; ADP leaves. Gold = H⁺. Blue = nucleophile (not hydride). White would be a detached PO₃ flyer — this page uses blue attack plus fadeSwap instead. This is not CDK1 mitosis and not hexokinase sugar phosphorylation.
Words used on screen — analog · cyclin occupancy · T-loop Analog — 1QMZ HHASPRK is a short model peptide, used here as a stand-in for a protein-Ser substrate. Cyclin occupancy — cyclin A is required for the active conformation; named, not swung. T-loop — Thr160-P (TPO) is CAK (CDK7) work, named, not this nucleophile. PDB numbering ≈ UniProt P24941 on the kinase domain.

Legend & Fidelity

Mechanism fidelity — measured vs. inferred The measured layer: 1QMZ (2.20 Å) with ATP, Mg, peptide, TPO160; Asp127 OD2 ⋯ PEP OG = 2.69 Å; PEP OG ⋯ ATP PG = 3.68 Å; Lys33 NZ ⋯ ATP O1A = 3.00 Å; Asp145 OD2 ⋯ MG = 1.91 Å. The inferred layer ([schematic]): phospho-peptide, ADP, transferring H⁺/nucleophile spheres, product leave, and ③/④ split. Binding order is compiled staging, not a kinetic fit. The protein mesh is static. Overlay phospho-peptide contacts are not geomClaims.
Disagreements on record (a) Peptide ≠ Rb ≠ p27. Crystal HHASPRK is a model analog. (b) 1FIN has no peptide — companion, not this mesh. (c) Concerted vs split. Compiled kinase writes deprotonation + γ-PO₃ transfer as one event; this page splits them (③ then ④) for 1-event/1-step teaching. (d) CDK1 / CDK4 / CDK6 are other genes. (e) TPO160 is CAK activation, not this nucleophile. (f) Inhibitors (palbociclib-class) are not this page. (g) No protein-domain swing — cyclin A does not morph.
Regulation — cyclin A · T-loop · isoforms Cyclin A is required occupancy for the active CDK2 conformation — named, not animated as domain motion. Thr160-P (TPO160) is CAK (CDK7) work, named, not this chemistry. Nuclear / cytosolic G1/S teaching isoform. Mitotic CDK1 is another gene. Wee1 / CDC25 act on CDK Tyr15 on other pages of this path.Source: UniProt P24941 · Brown 1999 PMID:10559988
Kinetics scope (no measured timecourse on this page) One ATP + protein-Ser/Thr → ADP + protein-Ser/Thr-P event is drawn, not a steady-state run. Compiled BRENDA values for EC 2.7.11.22 are not re-asserted here — no measured k_cat/K_m on this page [schematic]. Pair with a kinetics chapter.Source: BRENDA EC 2.7.11.22 — no k_cat/K_m re-asserted
Sequence Human CDK2 UniProt P24941 · NCBI Gene 1017. Screen uses 1QMZ PDB-author numbering (kinase domain ≈ UniProt). Chain A of the CDK2·cyclin A heterodimer.
Simulation map — what you see is what is written Setup = 1QMZ peptide cleft empty, cyclin A + TPO160 named (opaque, no autoplay). ① peptide analog moves in (crystal). ② ATP+Mg move in (crystal). ③ gold H⁺ + gold arrow OG → Asp127 OD2 (parks). ④ slow-mo: blue nucleophile + blue arrow OG → PG; peptide+ATP fade to phospho-peptide+ADP; parked gold H⁺ remains. ⑤ products leave opposite ways; cyclin A stays. Only these events move.
Sources — bibliography of this page S1 — PDB 1QMZ: human CDK2·cyclin A·ATP·Mg·peptide, 2.20 Å — public coordinates; measured OD2⋯OG = 2.69 Å · OG⋯PG = 3.68 Å · NZ⋯O1A = 3.00 Å · OD2⋯MG = 1.91 Å S2 — Brown et al., Nat Cell Biol 1999, PMID:10559988 — CDK2·cyclin A with ATP and a model peptide S3 — Sequence: UniProt P24941 (human CDK2) · NCBI Gene 1017 S4 — Kinetics: BRENDA EC 2.7.11.22 — 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., phospho-peptide identity, ADP after γ-transfer, H⁺ flight, product release), the pose is drawn schematically and labeled as such in the narration.

CDK2 kinasecyclin AONH⁺ (gold)nucleophile (blue)