title: Explication of interactions between HMGCR isoform 2 and various statins through In silico modeling and docking.
abstract: The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) catalyzes the conversion of HMG-CoA to mevalonate, a four-electron oxidoreduction that is the rate-limiting step in the synthesis of cholesterol and other isoprenoids. This study was designed to understand the mode of interactions of HMGCR isoform 2 with other statins. Hence, ligands such as Atorvastatin (DB01076), Lovastatin (DB00227), Fluvastatin (DB01095), Simvastatin (DB00641), Pravastatin (DB00175), Rosuvastatin (DB01098) and Cerivastatin (DB00439) were docked with enzymes HMGCR isoform 1 (pdb: 1DQ8) and modeled HMGCR isoform 2 (gi|196049380). Our homology modeling results were further processed to model the structure of human HMGCR isoform 2 and its accuracy was confirmed through RMS Z-scores (1.249). These interactions revealed that binding residues such as Arg515, Asp516, Tyr517 and Asn518 are found to be conserved in HMGCR isoform 2 with various statins. Our studies further concluded that Atorvastatin is most efficient inhibitor against both the isoforms of HMGCR whereas HMGCR isoform 2 shows less effectiveness with statins when compared with HMGCR isoform 1.
authors.affiliation: Enzyme Technology Laboratory, Department of Biotechnology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India.
authors.forename: M V K
authors.initials: MV
authors.lastname: Karthik
authors.forename: M V K N
authors.initials: MV
authors.lastname: Satya Deepak
authors.forename: Pratyoosh
authors.initials: P
authors.lastname: Shukla
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry / Q000378:metabolism*; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D010802:Phylogeny; D011485:Protein Binding; D015203:Reproducibility of Results; D040681:Structural Homology, Protein
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007527:Isoenzymes; C553220:HMGCR protein, human; D006903:Hydroxymethylglutaryl CoA Reductases