Activation Profile Analysis of CruCA4, an α-Carbonic Anhydrase Involved in Skeleton Formation of the Mediterranean Red Coral, Corallium rubrum
Open Access
Abstract
CruCA4, a coral α-carbonic anhydrase (CA, EC 4.2.1.1) involved in the biomineralization process of the Mediterranean red coral, Corallium rubrum, was investigated for its activation with a panel of amino acids and amines. Most compounds showed considerable activating properties, with a rather well defined structure–activity relationship. The most effective CruCA4 activators were d-His, 4-H2N-l-Phe, Histamine, Dopamine, Serotonin, 1-(2-Aminoethyl)-piperazine, and l-Adrenaline, with activation constants in the range of 8–98 nM. Other amines and amino acids, such as d-DOPA, l-Tyr, 2-Pyridyl-methylamine, 2-(2-Aminoethyl) pyridine and 4-(2-Aminoethyl)-morpholine, were submicromolar CruCA4 activators, with KA ranging between 0.15 and 0.93 µM. Since it has been shown that CA activators may facilitate the initial phases of in-bone mineralization, our study may be relevant for finding modulators of enzyme activity, which can enhance the formation of the red coral skeleton.Keywords
Funding Information
- Government of the Principality of Monaco and the Foundation Paul Hamel
This publication has 55 references indexed in Scilit:
- Induction of carbonic anhydrase in SaOS-2 cells, exposed to bicarbonate and consequences for calcium phosphate crystal formationBiomaterials, 2013
- Carbonic anhydrases: from biomedical applications of the inhibitors and activators to biotechnological use for CO2 captureJournal of Enzyme Inhibition and Medicinal Chemistry, 2013
- Molecular Cloning and Characterization of First Organic Matrix Protein from Sclerites of Red Coral, Corallium rubrumJournal of Biological Chemistry, 2012
- Carbonic anhydrase activators: Kinetic and X-ray crystallographic study for the interaction of d- and l-tryptophan with the mammalian isoforms I–XIVBioorganic & Medicinal Chemistry, 2008
- Carbonic Anhydrase Activators. Activation of Isozymes I, II, IV, VA, VII, and XIV with L‐ and D‐Histidine and Crystallographic Analysis of Their Adducts with Isoform II: Engineering Proton‐Transfer Processes within the Active Site of an EnzymeChemistry – A European Journal, 2006
- Carbonic Anhydrase Activators. Activation of Isoforms I, II, IV, VA, VII, and XIV with l- and d-Phenylalanine and Crystallographic Analysis of Their Adducts with Isozyme II: Stereospecific Recognition within the Active Site of an Enzyme and Its Consequences for the Drug DesignJournal of Medicinal Chemistry, 2006
- Carbonic Anhydrase Activators. XV. A Kinetic Study of the Interaction of Bovine Isozyme II with Pyrazoles, Bis- and Tris-azolyl-methanes.Biological and Pharmaceutical Bulletin, 1996
- Carbonic Anhydrase Activators. 3: Structure-Activity Correlations for a Series of Isozyme I1 ActivatorsJournal of Pharmaceutical Sciences, 1994
- Carbonic Anhydrase Activators. VII. Isozyme II Activation by Bisazolyl-methanes, -ethanes and Related Azoles.Biological and Pharmaceutical Bulletin, 1993
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970