of type 1 statins by the fluorophenyl group of type 2 statins. This group is responsible for additional polar interactions that causes tighter binding to the HMGR enzyme. Statins that belong to this group are: Fluvastatin (Figure 3) Cerivastatin Atorvastatin Rosuvastatin Lovastatin is derived from a fungus source and simvastatin and pravastatin are chemical modifications of lovastatin and as a result do not differ much in structure from lovastatin. All three are partially reduced napthylene ring structures. Simvastatin and lovastatin are inactive lactones which must be metabolized to their active hydroxy-acid forms in order to inhibit HMGR. Type 2 statins all exist in their active hydroxy-acid forms. Fluvastatin has indole ring structure, while atorvastatin and rosuvastatin have pyrrole and pyrimidine based ring structure respectively. The lipophilic cerivastatin has a pyridine-based ring structure. HMGR statin binding site Studies have shown that statins bind reversibly to the HGMR enzyme. The affinity of statins for HGMR enzyme is in the nanomolar range, while the natural substrate's affinity is in the micromolar range. Studies have shown that statins use the conformational flexibility of the HMGR enzyme that causes a shallow hydrophobic groove that the statins exploit and is used to accommodate their hydrophobic moieties. The specificity and the tight binding of statins is due to orientation and bonding interactions that form between the statin and the HMGR enzyme. Polar interactions are formed between the HMG-moiety and residues that are located in the cis loop of the enzyme. These polar interactions are between Ser684, Asp690, Lys691 and Lys692 (Figure 4). The terminal carboxylate of the HMG moiety forms a salt bridge with the cationic Lys735 of the enzyme. In addition to the polar interaction, Lys691 participates in a hydrogen bonding network with Glu559, Asp767 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 Leu562, Val683, Leu853, Ala856 and Leu857 and the statins. Type 2 statins form polar interaction between the fluorine atom on the fluorophenyl group and the guanidinium group of Arg590. In addition to these interactions atorvastatin and rosuvastatin also form unique hydrogen bonds between Ser565 residue and either a carbonyl oxygen atom (atorvastatin) or a sulfone oxygen atom (rosuvastatin). A unique polar interaction between the Arg568 side chain and the electronegative sulfone group on rosuvastatin makes it the statin that has the