Study of spermine as an inhibitor of carbonic anhydrase by anchoring to the zinc-coordinated water molecule.

Carbonic anhydrases(CAs) have been inhibited by different compounds such as phenols and coumarins. Usually, polyamines, have been used as activators of carbonic anhydrases enzymes, but they have been investigated recently as new inhibitors of human carbonic anhydrase. Spermine is a derivative of polyamines, which is a small aliphatic molecule found in fungi,archaea andplants[1, 2].In the present research we used the B3lyp method with the standard 6-31+g* basic set to predict the optimized geometries and interaction energies between inhibitors and CA active site.According to our calculated results poly aminescan be used as a suitable inhibitor, which has at least 7 atoms in the chain, with one free NH2group.Also the results show optimized spermine with threonine (Thr) amino acid have been established by different hydrogen bondings. Thus, an important point of this work is that we observed for the first time the anchoring of a primary amine (as charged ammonium moiety) to the zinc-bound solvent molecule of CA, through a network of hydrogen bonds involving also the conserved amino acidresidue Thr199.Finally, the good agreement between predicted results with X-ray crystallographic data confirm the reliability of selected methods for these kind of molecules.