Comparative modeling of PON2 and analysis of its substrate binding interactions using computational methods

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• 作者：Subramanian Barathi (1)
  Muralidaran Charanya (2)
  Shivashanmugam Muthukumaran (2)
  Narayanasamy Angayarkanni (1)
  Vetrivel Umashankar (2)
  
• 关键词：PON2 ; Ligands ; Modeling ; Docking ; HCTL
• 刊名：Journal of Ocular Biology, Diseases, and Informatics
• 出版年：2010
• 出版时间：June 2010
• 年：2010
• 卷：3
• 期：2
• 页码：64-72
• 全文大小：435KB
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• 作者单位：Subramanian Barathi (1)
  Muralidaran Charanya (2)
  Shivashanmugam Muthukumaran (2)
  Narayanasamy Angayarkanni (1)
  Vetrivel Umashankar (2)
  
  1. Department of Biochemistry and Cell Biology, Vision Research Foundation, Sankara Nethralaya, 18, College Road, Chennai, 600 006, India
  2. Center for Bioinformatics Sankara Nethralaya, Chennai, India
  

文摘

Paraoxonase (PON) constitutes a family of calcium-dependent mammalian enzymes comprising of PON1, PON2, and PON3. PON family shares ~60% sequence homology. These enzymes exhibit multiple activities like paraoxonase, arylesterase, and lactonase in a substrate dependent manner. Decreased PON activity has been reported in diseases like cardiovascular disease, atherosclerosis, and diabetes. Even though, PON2 is the oldest member of the family, PON1 is the only member studied in silico. In this study, the structure of PON2 was modeled using MODELLER 9v7 and its interactions with relevant ligands and it's physiological substrate homocysteine thiolactone was performed using AutoDock 4.0. The results reveal that PON1 and PON2 share common ligand binding patterns for arylesterase and lactonase activity, whereas in case of paraoxon binding, the residues involved in the interactions were different. Interestingly, the substrate HCTL was found to have the lowest free energy of binding (ΔG) and highest affinity for PON2 than PON1.