Adenylate cyclase

  Adenylate cyclase (EC 4.6.1.1, also known as adenylyl cyclase or AC) is a lyase enzyme.

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Types

There are nine known adenylate cyclases in mammals:

• ADCY1
• ADCY2
• ADCY3
• ADCY4
• ADCY5
• ADCY6
• ADCY7
• ADCY8
• ADCY9

Reaction

Adenylate cyclase catalyzes the conversion of ATP to 3',5'-cyclic AMP (cAMP) and pyrophosphate.

cAMP is an important molecule in eukaryotic signal transduction, a so-called second messenger. Adenylate cyclase can be activated or inhibited by G proteins, which are coupled to membrane receptors and thus can respond to hormonal or other stimuli.

Structure

  Adenylyl cyclase is a transmembrane protein. It passes through the plasma membrane twelve times.

The important parts for its function are located in the cytoplasm and can be subdivided into the N-terminus, C1a, C1b, C2a and C2b.

The C1 region exists between transmembrane helices six and seven and the C2 region follows transmembrane helix 12.

The C1a and C2a domains form a catalytic dimer where ATP binds and is converted to cAMP.

Regulation

Adenylate cyclase is stimulated by G proteins, and by forskolin, as well as other class-specific substrates:

• Isoforms I, III and VIII are also stimulated by Ca²⁺/calmodulin.
• Isoforms V and VI are inhibited by Ca²⁺ in a calmodulin-independent manner.

In neurons, adenylate cyclases are located next to calcium ion channels for faster reaction to Ca²⁺ influx; they are suspected of playing an important role in learning processes. This is supported by the fact that adenylate cyclases are coincidence detectors, meaning that they are only activated by several different signals occurring together.

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