Map · Cell biology · Cell-cycle control

Cell-cycle control G1 → S → G2 → M · CDK switches

Phosphorylation and its reversal: the activating and inhibitory CDK phosphates, the phosphatases that undo them, and Separase, the protease that opens sister chromatids. Layer 2 of three — pick a machine. Real crystal coordinates (RCSB PDB).

The six machines

KINASE · DRIVER

CDK2 (CDK1-class Ser/Thr kinase)

ATP + protein-Ser/Thr → ADP + protein-Ser/Thr-P

Cyclin-activated Ser/Thr kinase that drives S phase. In-line phosphoryl transfer; the T-loop and cyclin binding order the active cleft.

EC 2.7.11.22 · PDB 1QMZ

▶ OPEN SIMULATOR
→
pSer/Thr
KINASE · CAK

CDK7 (CDK-activating kinase)

ATP + CDK T-loop-Thr → ADP + CDK-Thr-P

The activating kinase of the CDK family: it phosphorylates the T-loop threonine that CDK2 needs to switch on.

EC 2.7.11.23 · PDB 1UA2

▶ OPEN SIMULATOR
→
T-loop-P
KINASE · BRAKE

Wee1 (inhibitory Tyr kinase)

ATP + CDK-Tyr15-OH → ADP + CDK-Tyr15-P

Puts the inhibitory phosphate on CDK Tyr15 to hold the cycle at the G2/M checkpoint. Atypical tyrosine kinase (EC 2.7.10).

EC 2.7.10.2 · PDB 1X8B

▶ OPEN SIMULATOR
→
pTyr15
PHOSPHATASE · RELEASE

Cdc25 (dual-specificity)

CDK-pTyr15 + H₂O → CDK-Tyr15 + Pᵢ

Erases Wee1's inhibitory mark to fire the G2/M transition. Cys-based dual-specificity phosphatase; a Cys-phosphate intermediate turns over through water.

EC 3.1.3.48 · PDB 1QB0

▶ OPEN SIMULATOR
→
Tyr15
PHOSPHATASE · ERASE

PP2A (PPP2CA, metal phosphatase)

protein-pSer + H₂O → protein-Ser + Pᵢ

Broad Ser/Thr protein phosphatase that reverses kinase marks across the cycle. Two-metal (di-Mn) centre activates the water.

EC 3.1.3.16 · PDB 2IE4

▶ OPEN SIMULATOR
→
Ser
PROTEASE · SEPARATION

Separase (ESPL1 / separin)

RAD21 (kleisin) cleaved at one site

Cysteine protease that cuts the cohesin kleisin RAD21 at anaphase, releasing sister chromatids. Not a phosphatase — a one-cut protease.

EC 3.4.22.49 · PDB 7NJ1

▶ OPEN SIMULATOR
⤷ A cycle is a set of reversible marks: Wee1 adds the brake, Cdc25 and PP2A remove it, CDK2/7 drive, Separase executes the split.