In-silico and Molecular Docking Studies on Germacrene A Synthase enzyme and sesuiterpene lactone (Lactucin) involved in antimalarial activity of Cichorium intybus

Abstract

Cichorium intybus, commonly known as Chicory, is a perennial herb with immense ethanomedical activity and being used in folklore medicine. Due to the presence of ample lactone, this plant has anti-malarial activity. The biosynthesis pathway of sequiterpene lactone (lactucin), which is considered to provide antimalarial activity to the plant, has Germacrene A Synthase as novel rate-limiting enzyme. This study demonstrates the structural and physiochemical properties of the enzyme Germacrene A Synthase through various bioinformatics approaches along with the docking studies. Through the in silico studies it was found that Germacrene A synthase protein interact with the lactucin with the lower energy − 7.3 kcal/mol and total 3 hydrogen bonds were formed by the Germacrene A Synthase at Gly45, Leu46, Tyr246 respectively while Leu41, Glu47, Tyr49, Asn43, Asp42, Ala50, Gln250, Leu249 amino acid residues act together through hydrophobic interactions. It was also found that the Hsp 90 protein of malaria parasite bound with lactucin with lower binding energy i.e. -5.5 kcal/mol. Two domain named terpene synthase has been determined which were found actively participate in the lactucin formation. Through CELLO, cellular localization of protein has been determined in the cytoplasm with maximum score of 2.829. The phylogenetic analysis showed that Germacrene A Synthase enzyme of chicory showing higher similarity with the Germacrene A synthase of Chichorium endivia and Lactuca sativa. Molecular docking results of lactucin and Hsp 90 protein of malarial parasites proceeding clinical trials with lactucin may give the more clue and justification for the active participation of lactucin as antimalarial compound. This study is progressively useful for further wet lab experiments and more in silico analysis to discover the mechanism of lactucin regulation by Germacrene A Synthase enzyme and also to analyze another regulating enzyme or the last enzyme involved in lactucin biosynthesis.