Carbonic anhydrase activators: l-Adrenaline plugs the active site entrance of isozyme II, activating better isoforms I, IV, VA, VII, and XIV

The activation of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) with l-adrenaline and histamine has been investigated by kinetic and X-ray crystallographic studies. l-Adrenaline behaves as a potent activator of isozyme CA I (activation constant of 90 nM), being a much weaker activator of isozyme CA II (activation constant of 96 μM). Isoforms CA IV, VA, VII, and XIV were activated by l-adrenaline with KAs in the range of 36–63 μM. The X-ray crystal structure of the CA II–l-adrenaline adduct revealed that the activator plugs the entrance of the active site cavity, obstructing it almost completely.