A plant oxysterol, 28-homobrassinolide binds HMGCoA reductase catalytic cleft: stereoselective avidity affects enzyme function

详细信息    查看全文

• 作者：Victor Mukherjee ; D. Vijayalaksmi ; Jagadeesh Gulipalli…
• 关键词：Phytosteroid ; 28 ; Homobrassinolide ; HMGCR ; Catalytic activity ; Sterol biosynthesis ; In silico ; Docking ; Gene expression
• 刊名：Molecular Biology Reports
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：43
• 期：10
• 页码：1049-1058
• 全文大小：1,196 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Animal Anatomy, Morphology and Histology
  Animal Biochemistry
  
• 出版者：Springer Netherlands
• ISSN：1573-4978
• 卷排序：43

文摘

Understanding the influence of ubiquitously present plant steroids on mammalian cell biology is currently of interest. Feedback inhibition of HMGCoA reductase (HMGCR) catalytic activity in the transformation of HMG-CoA to mevalonate is a significant regulatory step in sterol biosynthetic pathway. To assess the role of dietary steroids in this biochemical transformation, the phytosteroid isoform 28-homobrassinolide (28-HB), 90 % pure, obtained from Godrej Agrovet (India) was used to determine its effect on mammalian HMG-CoA reductase. Photometric assay of pure human and select rat tissue HMGCR post 28-HB oral feed, PCR-HMGCR gene expression, and in silico docking of 28-HB and HMGCoA on HMGCR protein template were carried out. Using an oral feed regimen of pure 28-HB, we noted a decrease of 16 % in liver, 17.1 % in kidney and 9.3 % in testicular HMGCR enzyme activity, 25 % in HMGCR gene expression and 44 % in the activity of pure human HMGCR due to this plant oxysterol. In silico docking studies yielded binding metrics for 28-HB-HMGCR lower than for HMGCoA-HMGCR, indicating stronger binding of HMGCR by this ligand. 28-HB exerts differential effects on rat tissue HMGCR, down regulates liver HMGCR gene expression and significantly inhibits HMGCR activity.