title: Carbonic anhydrase activators: L-Adrenaline plugs the active site entrance of isozyme II, activating better isoforms I, IV, VA, VII, and XIV.
abstract: 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 microM). Isoforms CA IV, VA, VII, and XIV were activated by L-adrenaline with K(A)s in the range of 36-63 microM. 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.
authors.affiliation: Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Temperini
authors.forename: Alessio
authors.initials: A
authors.lastname: Innocenti
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Antonio
authors.initials: A
authors.lastname: Mastrolorenzo
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D002256:Carbonic Anhydrases / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D020536:Enzyme Activators / Q000138:chemical synthesis* / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation
chemical_list: D020536:Enzyme Activators; D007527:Isoenzymes; D006632:Histamine; D002256:Carbonic Anhydrases; D004837:Epinephrine