Theoretical Investigation Of Carbonic Anhydrase Enzyme Catalytic Cycle As Biocatalyst in Carbon Dioxide Hydration

The hydration of carbon dioxide (CO۲) to bicarbonate ion and proton, a simple but essential reaction, is catalyzed by a family of ubiquitous zinc metalloenzymes known as carbonic anhydrase (CAs, EC ۴.۲.۱.۱) [۱, ۲]. This enzyme (CA) present in prokaryotes and eukaryotes and encoded to five classes: α-CAs, β-CAs, γ-CAs, δ-CAs and ζ-CAs [۳]. In the present research we explored the interaction between some of new activators and histamine as reference activator with human carbonic anhydrase cluster model, using quantum mechanical calculations, based on the DFT, quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO). The obtained results indicate that the activator molecule participates in proton transfer reactions by forming CA-activator complexes and enhances the formation of the active species of CA, the zinc hydroxide species. Moreover, bridging the two water molecules between activators molecules and CA active site, results in the formation of thermodynamically more stable CA-activator complexes. The results of our modeling could be useful in examining the long-range proton transfer processes and evaluating the role of hydrogen-bounded waternetworks. As CA activators recently emerged as interesting agents for enhancing cognition, in the management of carbonic anhydrasr deficiencies, or for therapy memory, these potent hCA activators may be considered of interest for in vivo investigations and for possible therapeutic applications. The good agreement between these theoretical results and the experimental data confirm the accuracy level of our calculations, able to predict the interaction site of newly designed CAAs, at least with the model active site of the enzyme.