Lanosterol synthase disease prevention and treatment (see Disease Relevance, below). Interest has grown in lanosterol synthase inhibitors as drugs to lower blood cholesterol and treat atherosclerosis. The widely popular statin drugs currently used to lower LDL (low-density lipoprotein) cholesterol function by inhibiting HMG-CoA reductase activity. Because this enzyme catalyzes the formation of precursors far upstream of (S)-2,3-epoxysqualene and cholesterol, statins may negatively influence amounts of intermediates required for other biosynthetic pathways (e.g. synthesis of isoprenoids, coenzyme Q). Thus, lanosterol synthase, which is more closely tied to cholesterol biosynthesis than HMG-CoA reductase, is an attractive drug target. Lanosterol synthase inhibitors are thought to
Discovery and development of statins Asp and the O5 hydroxyl group of the hydroxyglutartic acid component of the statins. Van der Waals interactions are formed between the hydrophobic side chains of the enzyme, which involve the Leu, Val, Leu, Ala and Leu and the statins. Type 2 statins form polar interaction between the fluorine atom on the fluorophenyl group and the guanidinium group of Arg. In addition to these interactions atorvastatin and rosuvastatin also form unique hydrogen bonds between Ser residue and either a carbonyl oxygen atom (atorvastatin) or a sulfone oxygen atom (rosuvastatin). A unique polar interaction between the Arg side chain and the