Cyclin-Dependent Kinase 7 - 3D Mechanism Simulator

Loading structural data… (1UA2)

References & Databases

START HERE — how to read ATP + CDK-T-loop-Thr → ADP + CDK-Thr-P A single CAK cartoon on the human CDK7 frame that exists: 1UA2 (3.02 Å), chain A, with ATP and phospho-Thr170 (TPO170). The T-loop peptide is a CDK-acceptor analog [schematic], not CDK2 and not TFIIH CTD. Phospho-peptide and ADP are [schematic]. No cyclin H / MAT1 on this mesh. No Mg in the deposit. Asp137 is the UniProt proton acceptor. Gold H⁺ parks on Asp137; blue is the Thr-OH nucleophile, not a hydride. TPO170 is CDK7 activation, named, not the nucleophile and not the CAK substrate. Overlay peptide distances are not geomClaims. TFIIH kinase (EC 2.7.11.23) is named, not shown.
Crystal structures PDB 1UA2 — human CDK7 + ATP + TPO170, 3.02 Å (Lolli 2004). Coordinates are public. Chains B/C/D are copies — teaching = chain A. Cyclin H / MAT1 are not on this deposit. Drug soaks are not this page.
Mechanism — Asp137 base, in-line γ-PO₃ onto T-loop Thr-OH Lolli et al., Structure 2004, PMID:15530371 — human CDK7 with ATP. UniProt P50613 ACT_SITE Asp137 is the proton acceptor; Lys41 orients ATP. No covalent phospho-enzyme. Product is CDK-T-loop-Thr-P, not a free sugar phosphate. Physiological acceptor teaching = CDK2 Thr160 — analog, not this mesh. Source: Lolli 2004 · UniProt P50613
0 — Setup: TPO170 stays, T-loop cleft shown empty 1UA2 holds CDK7, TPO170, and ATP. The T-loop cleft is shown empty so ordered binding can start. TPO170 stays as CDK7 activation, not a nucleophile and not the CAK substrate. Opaque, no autoplay. No cyclin H / MAT1.Source: PDB 1UA2
① — CDK T-loop analog presented A short CDK T-loop analog docks as a named stand-in for a CDK acceptor — [schematic], not CDK2 and not TFIIH CTD. Thr OG1 faces ATP γ-P. Overlay peptide Å are not geomClaims.Source: compiled CAK substrate identity · UniProt P50613
② — ATP docks Crystal ATP docks. Lys41 NZ ⋯ ATP O1A = 3.87 Å; Met94 N ⋯ ATP N1 = 2.77 Å on this deposit. No Mg is in 1UA2. Overlay peptide / ADP distances are not geomClaims.Source: 1UA2 ATP pose
③ — Asp137 deprotonates the Thr-OH (hypothetical, lit.-based) A gold H⁺ sphere rides a gold arrow from peptide OG1 to Asp137 OD2 and parks. Compiled kinase writes this proton transfer with the γ-PO₃ transfer; this page splits them.Source: UniProt P50613 ACT_SITE Asp137
④ — In-line γ-PO₃ transfer → phospho-T-loop (hypothetical, lit.-based) Blue nucleophile rides from peptide OG1 to ATP PG. Peptide + ATP fade in place to schematic phospho-T-loop and schematic ADP. Parked gold H⁺ stays on Asp137. Overlay phospho-peptide Å are not geomClaims. Slow-motion on purpose. No covalent phospho-enzyme.Source: compiled CDK kinase · UniProt P50613
⑤ — Products leave — TPO170 stays [schematic] Phospho-T-loop and ADP depart in opposite directions. Parked gold H⁺ leaves toward solvent. TPO170 stays as CDK7 activation. TFIIH kinase (EC 2.7.11.23) is named, not shown.Source: EC 2.7.11.22 net accounting

How to read this page — a first-pass primer First pass: Setup (TPO170 present, T-loop cleft empty, Asp137 ★) → ① T-loop analog docks → ② ATP docks → ③ gold H⁺ OG1 → Asp137 (parks) → ④ blue nucleophile OG1 → PG, peptide+ATP become phospho-T-loop+ADP → ⑤ products leave; TPO170 stays. Second pass: 3.87 / 2.77 Å are crystal facts on 1UA2; peptide, phospho-peptide, ADP, and the H spheres are [schematic]. Third pass: open “Disagreements” for analog vs CDK2, CAK vs TFIIH, TPO170 vs substrate, and concerted vs split.
Chemistry primer — CAK, not CDK2 G1/S CDK7 as CAK transfers ATP γ-phosphate onto a CDK T-loop Thr. Asp137 deprotonates the hydroxyl; the oxygen attacks γ-P in line; ADP leaves. Gold = H⁺. Blue = nucleophile (not hydride). This is not CDK2 G1/S phosphorylation of Rb, and not TFIIH phosphorylation of RNA polymerase II CTD (EC 2.7.11.23), which is named and not shown.
Words used on screen — analog · CAK · T-loop · TFIIH Analog — the T-loop peptide is a short model occupancy, used here as a stand-in for a CDK acceptor (CDK2 Thr160 teaching). CAK — CDK-activating kinase, this page’s EC 2.7.11.22 story. TPO170 — CDK7’s own T-loop phosphate, activation, not the substrate. TFIIH kinase — EC 2.7.11.23, named, not this mesh. PDB numbering ≈ UniProt P50613 on the kinase domain.

Legend & Fidelity

Mechanism fidelity — measured vs. inferred The measured layer: 1UA2 (3.02 Å) with ATP and TPO170; Lys41 NZ ⋯ ATP O1A = 3.87 Å; Met94 N ⋯ ATP N1 = 2.77 Å. The inferred layer ([schematic]): T-loop peptide, 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 peptide contacts are not geomClaims. No Mg is in this deposit.
Disagreements on record (a) Peptide ≠ CDK2 ≠ TFIIH CTD. The T-loop analog is a model occupancy. (b) CAK vs TFIIH kinase. EC 2.7.11.22 is this page; EC 2.7.11.23 is named, not shown. (c) TPO170 ≠ CAK substrate. Thr170-P is CDK7 activation. (d) 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. (e) No cyclin H / MAT1 on this mesh. (f) No protein-domain swing. (g) No Mg in 1UA2.
Regulation — cyclin H · MAT1 · T-loop · isoforms Cyclin H / MAT1 complete the CAK trimer in cells — not on this mesh, named. Thr170-P (TPO170) is CDK7 activation, named, not this chemistry. Nuclear teaching isoform. CDK2 G1/S is another page. TFIIH CTD kinase is another EC.Source: UniProt P50613 · Lolli 2004 PMID:15530371
Kinetics scope (no measured timecourse on this page) One ATP + CDK-T-loop-Thr → ADP + CDK-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 CDK7 UniProt P50613 · NCBI Gene 1022. Screen uses 1UA2 PDB-author numbering (kinase domain ≈ UniProt). Chain A of four copies.
Simulation map — what you see is what is written Setup = 1UA2 T-loop cleft empty, TPO170 named (opaque, no autoplay). ① T-loop analog moves in (schematic). ② ATP moves in (crystal). ③ gold H⁺ + gold arrow OG1 → Asp137 OD2 (parks). ④ slow-mo: blue nucleophile + blue arrow OG1 → PG; peptide+ATP fade to phospho-T-loop+ADP; parked gold H⁺ remains. ⑤ products leave opposite ways; TPO170 stays. Only these events move.
Sources — bibliography of this page S1 — PDB 1UA2: human CDK7·ATP·TPO170, 3.02 Å — public coordinates; measured NZ⋯O1A = 3.87 Å · N⋯N1 = 2.77 Å S2 — Lolli et al., Structure 2004, PMID:15530371 — crystal structure of human CDK7 S3 — Sequence: UniProt P50613 (human CDK7) · NCBI Gene 1022 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., T-loop peptide identity, phospho-peptide, ADP after γ-transfer, H⁺ flight, product release), the pose is drawn schematically and labeled as such in the narration.

CDK7 kinaseONH⁺ (gold)nucleophile (blue)