Activation modelling of beta- and gamma-class of carbonic anhydrase with amines and amino acids: Proton transfer process within the active site from thermodynamic point of view

作者：Ghiasi Mina^*; Hemati Somaye; Zahedi Mansour

来源：Computational and Theoretical Chemistry, 2017, 1109: 42-57.

DOI：10.1016/j.comptc.2017.03.041

• Carbonic anhydrase
• Activator
• Proton transfer
• Thermodynamic functions
• QM calculation
• Conformational analysis

Activation mechanisms of an inactive form of beta-carbonic anhydrase (beta-CA), [Zn+2(cys)(2)(his)(H2O)], and gamma-carbonic anhydrase (gamma-CA), [Co+2(his)(3)(H2O)], with amines and amino acids have been investigated extensively using quantum mechanical calculations. Two DFT methods including B3LY13/6-31G* and B3PW91/def2-SVP have been employed to calculate the details of electronic structure and electronic energy of different compounds and complexes through the reaction mechanism path. Conformational analysis of three activators of beta-CA, including D-phenylalanine, L-tyrosine and histamine and three activators of gamma-CA, including 2-pyridyl-methylamine, serotonin and L-phenylalanine, and a complex between different conformers of these activators and active center of beta- and gamma-carbonic anhydrase have been studied. In addition, thermodynamic functions for the total reaction and for the complexation between activators and beta- and gamma-CA are evaluated. The calculated results indicate that protonatable moiety of above mentioned activators participate in proton transfer from zinc (in beta-CA) and cobalt (in gamma-CA) bond water molecule and lead to the formation of the catalytically active species of CA enzyme, hydroxide coordinated to the zinc and cobalt ions. In all calculations, solvent effects have been considered in three solvents including water (epsilon = 78.9), 1-bromooctane (epsilon = 5) and 1, 2-ethanediol (epsilon = 40) using PCM model. Further, the interaction between the most stable and more effective activators conformers with beta- and gamma-CA in presence of water solvent were studied by employing explicit solvent model., 2017 Elsevier B.V.

• 出版日期2017-6-1