همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

Investigation of the interaction of syringic acid with carbonic anhydrase using molecular docking

نویسندگان :

Maliheh Sadat Atri¹ Mohammadreza Mohammadi²

1- دانشگاه مازندران 2- دانشگاه مازندران

کلمات کلیدی :

Carbonic anhydrase inhibitors،Zn2+،Glaucoma،Syringic acid،Docking

چکیده :

Carbonic anhydrases are a large group of zinc metalloenzymes that catalyze the physiological reaction of carbon dioxide hydration to bicarbonate and protons (1). Inhibition of the carbonic anhydrase enzyme is effective in the treatment of many diseases, including glaucoma and gastric ulcer (2). Recently, it has been found that carbonic anhydrase inhibitors can also be used as anti-obesity, anti-cancer and anti-diabetic drugs. Syringic acid is a phenolic compound that is found in olives, dates, pumpkins, grapes, honey and shows excellent antioxidant, antimicrobial, anti-obesity and anti-cancer activities (3). In this study, the molecular targets of syringic acid were first identified using the Swiss Target Prediction platform, and carbonic anhydrase family proteins were at the top of the list. Then using RCSB and CB-Dock2 websites, the active sites and their amino acids were identified and the interaction of syringic acid with carbonic anhydrases 2, 4, 9 and 12 was investigated by molecular docking method using Autodock software. The grid box was designed to be placed on the active site pocket of the enzyme. The results showed that syringic acid binds to the similar binding site on all these enzymes by hydrogen bonds and hydrophobic interactions. Some of these amino acids were common in all four enzymes, for example, histidine 119, that binds to Zn2+ ion in the native structure of carbonic anhydrase, is one of the amino acids that can form a hydrogen bond with syringic acid in these human carbonic anhydrase isoforms. The binding free energy range for carbonic anhydrases was calculated between -5.2 and -4.2 kcal/mol. The highest and lowest binding energy are related to carbonic anhydrases 2 and 12, respectively. Based on pervious experimental studies, phenols, including syringic acid, are anchored in the water molecule bound to (Zn2+) and inter the cavity of the active site of the enzyme, then bind to different amino acid residues (4). The results of this study suggest that syringic acid can bind to the active site and inhibit carbonic anhydrase enzyme, therefore as a bioactive compound is a suitable candidate for further studies to design new carbonic inhibitor drugs.