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

Abstract

The carbonic anhydrase is the enzyme that catalyzes the reversible hydration of carbon dioxide and 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 was discovered in marine diatoms to use naturally a cadmium ion as catalytic metal. In the present investigation 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 of zinc ion with cadmium does not entail significant differences in the catalytic performance of the enzyme. Our aim was to give further insight of the enzymatic work mechanism. Different possible reaction paths were considered for both metallic forms of the enzyme and comparison with previous studies concerning other carbonic anhydrases was made. The effects of the solvent on the energetics of the catalytic process, was also taken into account by means of a polarizable continuum model. The results obtained from density functional calculations, using a well consolidated mixing of exchange-correlation potential and basis set, and performed with a model of the active site designed on the basis of the X-ray crystal structure, proposed for both metal ions similar reaction pathways consisting in the nucleophilic attack by the metal bound hydroxide to the carbon dioxide with bicarbonate formation, in a next internal rotation of this last fragment, and then in the formation of a species ready for the product removal. Similar activation barriers were found in the rate determining steps that confirm the experimental indication concerning the comparable efficiency of the enzyme in the presence of a zinc or cadmium metal ion.

Comparison and Analysis of Zinc and Cobalt-Based Systems as Catalytic Entities for the Hydration of Carbon Dioxide

“…TS1 and TS3 maybe over stabilized when using the gas-phase geometries. A similar result occurred in a computational study of CO 2 being converted to HCO 3 - by a ζ-carbonic anhydrase containing either cadmium or zinc [52]. In the gas-phase, nucleophilic attack of CO 2 had the highest activation barrier, but when the dielectric constant was set to 4 (to better simulate the protein environment), the rotation barrier was rate-limiting.…”

“…The cobalt complexes are assumed to be in alkaline conditions which favor tetrahedral geometries and share similar characteristics to the zinc complexes [42], [43]. There have been several ab initio studies on the hydration of CO 2 by CAII [44], [45], [46], [47], [48], [49] but a thorough comparative study between Zn 2+ and other metals ions within CA have not been as widely studied [50], [51], [52]. Additionally, tris(4,5-di-n-propyl-2-imidazolyl)phosphine catalyzes the hydration of CO 2 , but the non-catalytic tris(4,5-dimethyl-2-imidazolyl)phosphine ( Ph ) was chosen for computational tractability and can provide insights into the reaction mechanism.…”

The Catalytic Mechanism of Human Transketolase

“…The protein environment was simulated via a polarizable continuum model (SCRF-PCM), [53] choosing a dielectric constant of ɛ = 4, as suggested in previous studies. [54][55][56][57] Finally, the Natural Bond Orbital (NBO) [58] analysis has been carried out on all stationary points.…”

How Can Methanol Dehydrogenase from Methylacidiphilum fumariolicum Work with the Alien CeIII Ion in the Active Center? A Theoretical Study

“…The solvation energies were obtained from single point calculations performed on the optimized geometries with the more extended basis set 6–311+G(2d,2p)|SDD. The choice of the dielectric constant ϵ =4 is usually considered to be a good representation of protein surrounding . For the potential energy surfaces (PESs), the final solvation energies reported include the ZPE corrections.…”