Quantum mechanical study of human carbonic anhydrase II in complex with polyamines as novel inhibitors: Kinetic and thermodynamic investigation

Abstract

Spermine and spermidine polyamines are investigated as a new class inhibitors of different carbonic anhydrase (CA) isoforms using DFT calculations. Our results indicate these two polyamines, inhibited the human carbonic anhydrase with very different inhibition profiles compared to other inhibitors. According to calculated results, studied polyamines are anchored to the non-protein zinc ligand (hydroxyl ion) by means of a hydrogen bond of 2.6 Å involving one of terminal ammonium group and an intermediate complex is formed, [(his)3Zn(II)(OH)/polyamine], which is in good agreement with experimental data. By transferring a proton from the terminal ammonium group of polyamine inhibitor to the oxygen atom of the hydroxyl group, the active form of the CA enzyme converted to the inactive form. Finally, the HOMO-LUMO and AIM analysis have been done to understand the details of interaction between studied polyamines and CA active center in intermediate complex in water phase.