1w6k: Difference between revisions

==Overview==

In higher organisms the formation of the steroid scaffold is catalysed, exclusively by the membrane-bound oxidosqualene cyclase (OSC; lanosterol, synthase). In a highly selective cyclization reaction OSC forms lanosterol, with seven chiral centres starting from the linear substrate, 2,3-oxidosqualene. Valuable data on the mechanism of the complex, cyclization cascade have been collected during the past 50 years using, suicide inhibitors, mutagenesis studies and homology modelling., Nevertheless it is still not fully understood how the enzyme catalyses the, reaction. Because of the decisive role of OSC in cholesterol biosynthesis, it represents a target for the discovery of novel anticholesteraemic drugs, that could complement the widely used statins. Here we present two crystal, structures of the human membrane protein OSC: the target protein with an, inhibitor that showed cholesterol lowering in vivo opens the way for the, structure-based design of new OSC inhibitors. The complex with the, reaction product lanosterol gives a clear picture of the way in which the, enzyme achieves product specificity in this highly exothermic cyclization, reaction.

==About this Structure==

[[Category: steroid biosynthesis]]