Carbonic anhydrase activators. Activation of the membrane-associated isoform XV with amino acids and amines.
An activation study of the membrane-associated carbonic anhydrase (CA, EC 4.2.1.1) isoform XV with a series of natural and non-natural amino acids and aromatic/heterocyclic amines is reported. Murine CA XV was strongly activated by some amino acids (d-Phe, l-/d-DOPA, d-Trp, l-Tyr) and amines (dopamine, serotonin, l-adrenaline and 4-(2-aminoethyl)-morpholine) with activation constants in the range of 4.0-9.5muM. l-/d-His, l-Phe, histamine and several other heterocyclic amines showed less efficient activation (K(A)s in the range of 11.6-33.4muM). The activation profile of CA XV is quite different from that of the cytosolic isoforms CA I and II or the membrane-associated CA IV. All mammalian isoforms CA I-XV are thus characterized for their interaction with this set of amino acid and amine activators, some of which are biogenic amines or neurotransmitters present in sufficiently high amounts in various tissues for exerting significant biologic responses.
Innocenti
Alessio
A
Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Firenze, Italy.
Hilvo
Mika
M
Parkkila
Seppo
S
Scozzafava
Andrea
A
Supuran
Claudiu T
CT
D000588:Amines / Q000737:chemistry*; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D002256:Carbonic Anhydrases / Q000737:chemistry / Q000378:metabolism*; D020536:Enzyme Activators / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
D000588:Amines; D000596:Amino Acids; D020536:Enzyme Activators; D020033:Protein Isoforms; D011994:Recombinant Proteins; D002256:Carbonic Anhydrases; C507974:carbonic anhydrase XV, mouse