Role of water in cyclooxygenase catalysis and design of anti-inflammatory agents targeting two sites of the enzyme.

ABSTRACT: While designing the anti-inflammatory agents targeting cyclooxygenase-2 (COX-2), we first identified a water loop around the heme playing critical role in the enzyme catalysis. The results of molecular dynamic studies supported by the strong hydrogen-bonding equilibria of the participating atoms, radical stabilization energies, the pK_a of the H-donor/acceptor sites and the cyclooxygenase activity of pertinent muCOX-2 ravelled the working of the water-peptide channel for coordinating the flow of H·/electron between the heme and Y385. Based on the working of H·/electron transfer channel between the 12.5 Å distant radical generation and the radical disposal sites, a series of molecules was designed and synthesized. Among this category of compounds, an appreciably potent anti-inflam

SUBMITTER: Kaur M 

PROVIDER: S-EPMC7329864 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature