Adenylyl cyclase

[2] It is the most polyphyletic known enzyme: six distinct classes have been described, all catalyzing the same reaction but representing unrelated gene families with no known sequence or structural homology.

[4] All classes of adenylyl cyclase catalyse the conversion of adenosine triphosphate (ATP) to 3',5'-cyclic AMP (cAMP) and pyrophosphate.

The cAMP produced by AC then serves as a regulatory signal via specific cAMP-binding proteins, either transcription factors, enzymes (e.g., cAMP-dependent kinases), or ion transporters.

It was observed that E. coli deprived of glucose produce cAMP that serves as an internal signal to activate expression of genes for importing and metabolizing other sugars.

[5] These adenylyl cyclases are toxins secreted by pathogenic bacteria such as Bacillus anthracis, Bordetella pertussis, Pseudomonas aeruginosa, and Vibrio vulnificus during infections.

[6] These bacteria also secrete proteins that enable the AC-II to enter host cells, where the exogenous AC activity undermines normal cellular processes.

A Nobel Prize was awarded to Earl Sutherland in 1971 for discovering the key role of AC-III in human liver, where adrenaline indirectly stimulates AC to mobilize stored energy in the "fight or flight" response.

Adenylyl cyclases are often activated or inhibited by G proteins, which are coupled to membrane receptors and thus can respond to hormonal or other stimuli.

[11] Photoactivated adenylyl cyclase (PAC) was discovered in Euglena gracilis and can be expressed in other organisms through genetic manipulation.

Shining blue light on a cell containing PAC activates it and abruptly increases the rate of conversion of ATP to cAMP.

[2] It is also regulated by forskolin,[11] as well as other isoform-specific effectors: In neurons, calcium-sensitive adenylyl 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 adenylyl cyclases are coincidence detectors, meaning that they are activated only by several different signals occurring together.

[15] In peripheral cells and tissues adenylyl cyclases appear to form molecular complexes with specific receptors and other signaling proteins in an isoform-specific manner.

These are the smallest of the AC enzyme classes; the AC-IV (CyaB) from Yersinia is a dimer of 19 kDa subunits with no known regulatory components (PDB: 2FJT​).

Adenylyl cyclase catalyzes the conversion of ATP to 3',5'-cyclic AMP .
Structure of adenylyl cyclase