title: In silico and in vitro Studies on Begomovirus Induced Andrographolide Biosynthesis Pathway in Andrographis Paniculata for Combating Inflammation and Cancer.
abstract: Andrographolide and neoandrographolide are major bioactive molecules of Andrographis paniculata, a well-known medicinal plant. These molecules exhibited varying degrees of anti-inflammatory and anticancer activities in-vitro and in-vivo. Role of begomovirus protein C2/TrAP in biosynthesis of andrographolide was identified through molecular modeling, docking and predicted results were substantiated by in vitro studies. Homology molecular modeling and molecular docking were performed to study the binding conformations and different bonding behaviors, in order to reveal the possible mechanism of action behind higher accumulation of andrographolide. It was concluded that C2/TrAP inhibit the activation of SNF1-Related Protein Kinase-1 (SnRK1) in terpenoid pathway and removes the negative regulation of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) by SnRK1, leading to higher accumulation of andrographolide and neoandrographolide in begomovirus infected plants. The binding site residues of SnRK1 docked with C2/TrAP were found to be associated with ATP binding site, substrate binding site and activation loop. Predicted results were also validated by HPTLC. This study provides important insights into understanding the role of viral protein in altering the regulation of biosynthesis of andrographolide and could be used in future research to develop biomimetic methods for increasing the production of such phytometabolites having anti-cancerous and anti-inflammatory properties.
authors: Plant Pathology Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, U.P. - 226015, India.
authors: Asifa
authors: A
authors: Khan
authors: Metabolic & Structural Biology Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, U.P. - 226015, India.
authors: Pooja
authors: P
authors: Sharma
authors: Metabolic & Structural Biology Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, U.P. - 226015, India.
authors: Feroz
authors: F
authors: Khan
authors: Analytical Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, U.P. - 226015, India.
authors: P V
authors: PV
authors: Ajayakumar
authors: Analytical Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, U.P. - 226015, India.
authors: Karuna
authors: K
authors: Shanker
authors: Plant Pathology Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, U.P. - 226015, India. samad_cimap@yahoo.co.in.
authors: Abdul
authors: A
authors: Samad
mesh_terms: D020816:Amino Acid Motifs; D035685:Andrographis / Q000737:chemistry* / Q000378:metabolism / Q000821:virology; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000096:biosynthesis / Q000737:chemistry*; D053839:Begomovirus / Q000502:physiology*; D053898:Biosynthetic Pathways; D020134:Catalytic Domain; D004224:Diterpenes / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D062105:Molecular Docking Simulation; D010935:Plant Diseases / Q000821:virology; D010940:Plant Proteins / Q000737:chemistry; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011494:Protein Kinases / Q000737:chemistry; D013816:Thermodynamics; D014764:Viral Proteins / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D010940:Plant Proteins; D014764:Viral Proteins; C030419:andrographolide; D011494:Protein Kinases
keywords: SnRK1 protein kinase; anti-cancerous; anti-inflammatory; docking; viral protein C2/TrAP