Catalytic activity of a -class zinc and cadmium containing carbonic anhydrase. Compared work mechanisms

The carbonic anhydrase is the enzyme that catalyzes the reversible hydration of carbon dioxideand represents one of the most ancient proteins to which a plethora of works was devoted.The three main classes rely on zinc ion for activity. Most recently a new class of CA wasdiscovered in marine diatoms to use naturally a cadmium ion as catalytic metal. In the presentinvestigation we focused our attention on a carbonic anhydrase cambialistic enzyme (CDCA1)belonging to this new class. The study was inspired by the discovery that the replacement ofzinc ion with cadmium does not entail significant differences in the catalytic performance of theenzyme. Our aim was to give further insight of the enzymatic work mechanism. Different possiblereaction paths were considered for both metallic forms of the enzyme and comparison withprevious studies concerning other carbonic anhydrases was made. The effects of the solvent onthe energetics of the catalytic process, was also taken into account by means of a polarizablecontinuum model. The results obtained from density functional calculations, using a wellconsolidated mixing of exchange–correlation potential and basis set, and performed with a modelof the active site designed on the basis of the X-ray crystal structure, proposed for both metalions similar reaction pathways consisting in the nucleophilic attack by the metal bound hydroxideto the carbon dioxide with bicarbonate formation, in a next internal rotation of this lastfragment, and then in the formation of a species ready for the product removal. Similaractivation barriers were found in the rate determining steps that confirm the experimentalindication concerning the comparable efficiency of the enzyme in the presence of a zincor cadmium metal ion.