Explication of interactions between HMGCR isoform 2 and various statins through In silico modeling and docking

  • Authors:

  • M. V. K. Karthik;M. V. K. N. Satya Deepak;Pratyoosh Shukla

  • Affiliations:

  • Enzyme Technology Laboratory, Department of Biotechnology, Birla Institute of Technology, Mesra, Ranchi 835215, Jharkhand, India;Department of Pharmacy, SASTRA University, Thanjavur, Tamilnadu;Enzyme Technology Laboratory, Department of Biotechnology, Birla Institute of Technology, Mesra, Ranchi 835215, Jharkhand, India

  • Venue:
  • Computers in Biology and Medicine
  • Year:
  • 2012

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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.