Table of Contents
Metal-Based Drugs
Volume 4, Issue 4, Pages 221-227
http://dx.doi.org/10.1155/MBD.1997.221

Carbonic Anhydrase Activators. Part 191 Spectroscopic and Kinetic Investigations for the Interaction of Isozymes I and II With Primary Amines

Università degli Studi, Laboratorio di Chimica Inorganica e Bioinorganica, Via Gino Capponi 7, Firenze I-50121, Italy

Received 2 June 1997; Accepted 12 June 1997

Copyright © 1997 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The interactions of Zn(II)- and Co(II)-substituted carbonic anhydrase (CA) isozymes I and II with amine type activators such as histamine, serotonin, phenetylamine dopamine and benzylhydrazine have been investigated kinetically, and spectroscopically. All of such activators are of the non-competitive type towards CO2 hydration and 4-nitrophenylacetate hydrolysis for both human isozymes (HCA I and HCA II). The electronic spectra of the adducts of Co(II)CA with amine activators are similar to the spectrum of the previously reported Co(II)CAII-phenol adduct, the only known competitive inhibitor towards CO2 hydration, where the phenol molecule binds into the hydrophobic pocket of the active site. This is a direct spectroscopic evidence that the activator molecules bind within the active site, but not directly to the metal ion. Recent X-ray crystallographic data for the adduct of HCA II with histamine show that the activator molecule is bound at the entrance of the active site cavity, near to residues His 64, Asn 62 and Gln 92, where actively aids in shuttling protons between the active site and the environment. Similar arrangements probably occur for the other activators reported in the present paper.