title: In silico study of binding motifs in squalene synthase enzyme of secondary metabolic pathway of solanaceae [corrected].
abstract: Solanaceae is an important family with several plants of medicinal importance. These medicinal plants have distinctive pathways for secondary metabolite biosynthesis. In most of the plants, two important compounds, dimethylallyl diphosphate and isopentenyl diphosphate, synthesize isoprenoid or terpenoids. Squalene synthase (SQS) is a key enzyme of the biosynthesis of isoprenoid (farnesyl pyrophosphate (FPP) → squalene). Withania somnifera (ashwagandha), an important medicinal plant of family solanaceae produces withanolides. Withanolides are secondary metabolites synthesized through isoprenoid pathway. In this study, 13 SQS protein sequences from the plants of solanacae family and Arabidopsis thaliana were analyzed. The conserved domains in corresponding sequences were searched. The multiple sequence alignment of conserved domains revealed the important motifs and identified the residue substitution in each motif. Our result further indicated that residue substitution in motifs might not lead to functional variation, although it may affect the binding affinity of Mg(++), FPP and NAD(P)H. In addition, the homology modelling of SQS enzyme of W. somnifera was done for the prediction of three-dimensional structure. Molecular docking study of considered substrates with WsSQS was performed and the docked structure were analyzed further. The docked structures showed binding affinity for motif 2 of WsSQS. Our analysis revealed that 29 residues of motif 2 might be important for catalytic/functional activity of SQS enzyme of W. somnifera. This study may provide an understanding of metabolic pathways responsible for the production of secondary metabolites. The motifs may play a key role in regulating the pathway towards enhanced production of metabolites.
authors.affiliation: Biotechnology Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Post Office CIMAP, Lucknow, 226015, India, 0804sanchita@gmail.com.
authors.lastname: Sanchita
authors.forename: Garima
authors.initials: G
authors.lastname: Singh
authors.forename: Ashok
authors.initials: A
authors.lastname: Sharma
mesh_terms: D000595:Amino Acid Sequence; D017360:Arabidopsis / Q000201:enzymology; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics*; D053898:Biosynthetic Pathways / Q000235:genetics*; D016000:Cluster Analysis; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000235:genetics* / Q000378:metabolism*; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010802:Phylogeny; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D032341:Withania / Q000201:enzymology*
chemical_list: D013186:Farnesyl-Diphosphate Farnesyltransferase
references.citation: Phytochemistry. 2005 Apr;66(8):869-77
references.pmid: 15845405
references.citation: Nucleic Acids Res. 2011 Jan;39(Database issue):D225-9
references.pmid: 21109532
references.citation: J Comput Chem. 2009 Dec;30(16):2785-91
references.pmid: 19399780
references.citation: Phytochemistry. 2008 Feb;69(4):1000-4
references.pmid: 18061221
references.citation: PLoS One. 2012;7(5):e37764
references.pmid: 22701533
references.citation: Mol Biol Evol. 2011 Oct;28(10):2731-9
references.pmid: 21546353
references.citation: Mol Cancer Ther. 2010 Jan;9(1):202-10
references.pmid: 20053782
references.citation: Planta. 2011 Feb;233(2):343-55
references.pmid: 21053012
references.citation: J Biol Chem. 1993 Jun 15;268(17):12825-36
references.pmid: 8509416
references.citation: Int J Mol Sci. 2013 Jan 29;14(2):2753-73
references.pmid: 23434646
references.citation: Biochemistry. 2000 Feb 22;39(7):1748-60
references.pmid: 10677224
references.citation: J Biol Chem. 2000 Sep 29;275(39):30610-7
references.pmid: 10896663
references.citation: Gene. 2012 May 10;499(1):25-36
references.pmid: 22425978
references.citation: Ciba Found Symp. 1990;154:126-34; discussion 135-9
references.pmid: 2086033
references.citation: J Biomol Struct Dyn. 2013;31(8):874-87
references.pmid: 22970930
references.citation: Plant Cell Physiol. 2004 Aug;45(8):976-84
references.pmid: 15356323
references.citation: Methods Enzymol. 2003;374:461-91
references.pmid: 14696385
references.citation: Biochim Biophys Acta. 2007 Sep;1774(9):1199-207
references.pmid: 17704015
references.citation: Comp Funct Genomics. 2004;5(3):285-91
references.pmid: 18629162
references.citation: Plant Cell Physiol. 2011 Jan;52(1):125-37
references.pmid: 21134898
references.citation: Comput Appl Biosci. 1995 Dec;11(6):681-4
references.pmid: 8808585
references.citation: Molecules. 2009 Jul 03;14(7):2373-93
references.pmid: 19633611
references.citation: Planta. 2009 May;229(6):1243-52
references.pmid: 19283408
references.citation: Mol Biol Rep. 2012 Sep;39(9):8803-12
references.pmid: 22718506
references.citation: Methods Mol Biol. 1997;70:119-29
references.pmid: 9089607