Author(s): D. Jeya Sundara Sharmila and Swathi Jogi
Oxidosqualene cyclase (OSC) is an eukaryotic monotopic membrane protein which converts oxidosqualene to lanosterol, forming the steroid scaffold in a single reaction. Prokaryotes posses an enzyme similar to OSC that is Squalene-Hopene Cyclase (SHC). Unlike SHC, OSC can only accept 2,3-oxidosqualene as the substrate. Both these enzymes have an lipophilic channel which leads into the active site through an narrow constriction. The lipophilic channel plays an important role in the entry of substrate into the active site. Although the architecture of the lipophilic channel is clear from the crystal structure, its role in substrate-enzyme interaction is still far being fully understood. The insilico mutation studies on the active site amino acid residue Cys456, of the lipophilic channel has revelead that the double mutation of Cys456Ser and active site residue Asp455Cys would block the entry of substrate into the active site. Thus leading to the loss of ligand and active site interactions.