Map · Cell biology · Second messengers

Second messengers cAMP / cGMP / IP₃ / DAG

Small molecules that carry a signal inside the cell. Cyclases build them from nucleotide triphosphates, phosphodiesterases destroy them, and PLCβ1 splits a lipid into two at once. Layer 2 of three — pick a machine. Real crystal coordinates (RCSB PDB).

The four machines

CYCLASE · MAKE cAMP

Adenylyl cyclase (AC)

ATP → cAMP + PPᵢ

Turns ATP into the second messenger cAMP. A pair of metal ions activate the ATP 3'-OH for an intramolecular attack that closes the cyclic ring.

EC 4.6.1.1 · PDB 1CJK

▶ OPEN SIMULATOR
→
cAMP
CYCLASE · MAKE cGMP

Guanylate cyclase (soluble sGC)

GTP → cGMP + PPᵢ

Same trick on GTP to make cGMP — the messenger of nitric-oxide signalling. A heme senses NO before the catalytic domain fires.

EC 4.6.1.2 · PDB 6JT2

▶ OPEN SIMULATOR
→
cGMP
PHOSPHODIESTERASE · BREAK

PDE4D (cAMP phosphodiesterase)

cAMP + H₂O → AMP

The off-switch: hydrolyses cAMP's cyclic phosphodiester to plain AMP. Bimetallic centre plus a general base activate the water.

EC 3.1.4.53 · PDB 1TB7

▶ OPEN SIMULATOR
→
AMP
PHOSPHOLIPASE · SPLIT

PLCβ1 (phospholipase C)

PIP₂ + H₂O → IP₃ + DAG

Cuts the membrane lipid PIP₂ into two messengers at once: IP₃ (released) and DAG (stays in the membrane). One reaction, two signals.

EC 3.1.4.11 · PDB 1DJX

▶ OPEN SIMULATOR
⤷ Build and destroy: cyclases create cAMP/cGMP from NTPs, PDE4 removes cAMP, and PLCβ1 generates two messengers from one lipid cut.