title: Molecular docking of Glyceroneogenesis pathway intermediates with Peroxisome Proliferator- Activated Receptor-Alpha (PPAR-α).
abstract: Peroxisome proliferator-activated receptor alpha (PPAR-α) belongs to the nuclear receptor superfamily of proteins. It is one of the principle regulators of metabolism and lipid homeostasis whose malfunction leads to complications including obesity and type 2 diabetes. In the adipose tissue, glyceroneogenesis is a unique pathway through which pyruvate is converted into glycerol-3- phosphate (G3P) in a multistep process. Previous findings demonstrated that glyceroneogenesis regulates triacylglycerol synthesis and adipogenesis. This led us to hypothesize that one of the pathway intermediate is physiologically relevant PPAR-α ligand. In the present study using in silico docking, we proved that glycerate, dihydroxy acetone phosphate, glyceraldehyde-3-phosphate, and G3P are key glyceroneogenesis pathway intermediates which bind to PPAR-α. They bind PPAR-α with comparable binding energy and docking score to that of (2s)-2-ethoxy-3-[4-(2-{4-[(methylsulfonyl)oxy]phenyl}ethoxy)phenyl]propanoic acid(AZ-2), a synthetic high affinity ligand of PPAR-α. These intermediates could be studied further as potential physiologically relevant activators of PPAR-α in vitro and in vivo.
authors.affiliation: Department of Zoology, Yogi Vemana University, Kadapa - 516 003, Andhra Pradesh, India.
authors.forename: Parasuraman Aiya
authors.initials: PA
authors.lastname: Subramani
authors.forename: Kalpana
authors.initials: K
authors.lastname: Panati
authors.forename: Venkata Ramireddy
authors.initials: VR
authors.lastname: Narala
keywords: PPAR-α; endogenous ligands; glyceroneogenesis; in silico docking
references.citation: J Comput Chem. 2004 Oct;25(13):1605-12
references.pmid: 15264254
references.citation: Structure. 2001 Aug;9(8):699-706
references.pmid: 11587644
references.citation: Annu Rev Physiol. 2003;65:261-311
references.pmid: 12518001
references.citation: Indian J Pharm Sci. 2011 Mar;73(2):159-64
references.pmid: 22303058
references.citation: J Chem Inf Model. 2007 Jul-Aug;47(4):1599-608
references.pmid: 17585856
references.citation: Nat Rev Endocrinol. 2010 Aug;6(8):454-63
references.pmid: 20567246
references.citation: Biochim Biophys Acta. 2007 Aug;1771(8):915-25
references.pmid: 17317294
references.citation: J Biol Chem. 2004 Aug 20;279(34):36093-102
references.pmid: 15190061
references.citation: PLoS One. 2012;7(6):e38546
references.pmid: 22685582
references.citation: J Neuroinflammation. 2012 Feb 18;9:34
references.pmid: 22339770
references.citation: J Lipid Res. 1969 Sep;10(5):521-7
references.pmid: 5808825
references.citation: Cell. 1999 Apr 16;97(2):161-3
references.pmid: 10219237
references.citation: J Clin Invest. 2004 Jul;114(1):94-103
references.pmid: 15232616
references.citation: J Biol Chem. 2010 Jul 16;285(29):22067-74
references.pmid: 20400503
references.citation: J Lipid Res. 1996 May;37(5):907-25
references.pmid: 8725145
references.citation: J Biol Chem. 2008 Oct 10;283(41):27565-27574
references.pmid: 18662986
references.citation: Endocrinology. 2011 May;152(5):1829-38
references.pmid: 21406501
references.citation: J Biol Chem. 2000 Jun 2;275(22):16638-42
references.pmid: 10828060
references.citation: J Biol Chem. 2003 Aug 15;278(33):30413-6
references.pmid: 12788931