An Asymmetric Pattern in Binding of Prostaglandin Endoperoxide H Synthases to their Inhibitors and its Implications for Enzyme Catalysis and Allosteric Regulation

Abstract

Proteins experience some conformational changes upon ligand bindings and their effects on protein functions are displayed in various ways. Crystallographic data of protein/ligand complexes are essential in exploring this issue; structural determinations of the complexes of interest, however, are often challenging and docking procedure can be carefully designed as an adequate substitute. Prostaglandin endoperoxide H synthases (PGHSs), also known as cyclooxygenases, have been investigated recently in an attempt to understand their half-of-sites enzyme activity and consequent biological significance. PGHSs are heme-containing proteins exist in solution as sequence homodimer, but once their catalytic cycle of cyclooxygenase/peroxidase is initiated, they behave functionally as a heterodimeric manner. Biochemical approach to solve this puzzle has been intensively attempted and suggested their interchangeability of structurally distinct two monomers. This paper presents an analysis of PGHS-ligand interactions upon binding either experimentally or virtually and predicts its biological implications.