title: Identification of a novel and potent inhibitor of phospholipase A(2) in a medicinal plant: crystal structure at 1.93Å and Surface Plasmon Resonance analysis of phospholipase A(2) complexed with berberine.
abstract: Crystal of Russell Viper venom phospholipase A(2) complexed with an isoquinoline alkaloid, berberine from a herbaceous plant Cardiospermum halicacabum, was prepared and its structure was solved by X-ray crystallography. The crystal diffracted up to 1.93Å and the structure solution clearly located the position of berberine in the active site of the enzyme. Two hydrogen bonds, one direct and the other water mediated, were formed between berberine and the enzyme. Gly 30 and His 48 made these two hydrogen bonds. Additionally, the hydrophobic surface of berberine made a number of hydrophobic contacts with side chains of neighboring amino acids. Surface Plasmon Resonance studies revealed strong binding affinity between berberine and phospholipase A(2). Enzyme inhibition studies proved that berberine is a competitive inhibitor of phospholipase A(2). It was inferred that the isoquinoline alkaloid, berberine, is a potent natural inhibitor of phospholipaseA(2).
authors.affiliation: Department of Biotechnology & Microbiology, Kannur University, Palayad, Kerala 670661, India.
authors.forename: D Naveen
authors.initials: DN
authors.lastname: Chandra
authors.forename: G K
authors.initials: GK
authors.lastname: Prasanth
authors.forename: Nagendra
authors.initials: N
authors.lastname: Singh
authors.forename: Sanjit
authors.initials: S
authors.lastname: Kumar
authors.forename: O
authors.initials: O
authors.lastname: Jithesh
authors.forename: C
authors.initials: C
authors.lastname: Sadasivan
authors.forename: Sujatha
authors.initials: S
authors.lastname: Sharma
authors.forename: Tej P
authors.initials: TP
authors.lastname: Singh
authors.forename: M
authors.initials: M
authors.lastname: Haridas
mesh_terms: D000818:Animals; D001599:Berberine / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray / Q000379:methods*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D017840:Daboia / Q000378:metabolism; D029631:Sapindaceae / Q000737:chemistry*; D020349:Surface Plasmon Resonance
chemical_list: D004791:Enzyme Inhibitors; D001599:Berberine; D010741:Phospholipases A