title: Caffeoylquinic acids competitively inhibit pancreatic lipase through binding to the catalytic triad.
abstract: Caffeoylquinic acid and its isomers inhibited porcine Pancreatic Lipase (PL) activity according to a competitive mode where binding and interaction with the catalytic triad of Ser153, His264 and Asp177 simultaneously occurred. The IC50 values under which 3-caffeoylquinic acid (CQA) and its isomers 4-, 5-CQA, 3,4-, 3,5- and 4,5-diCQA inhibited half of the porcine PL activity were 1.10, 1.23, 1.24, 0.252, 0.591 and 0.502 mM, respectively. The binding affinities in the range from -8.4 to -9.5 kCal/mol were well predicted from docking, which showed a high linear correlation coefficient of 0.893 and Spearman correlation of 1.0 with log(IC50) values. Caffeoylquinic acid and its isomers were stabilized by hydrogen bond and hydrophobic interaction in the binding pocket. This finding provided molecular mechanism of coffee and other natural food or drink containing caffeoylquinic acid and its isomers against lipase activity.
authors.affiliation: College of Food Science and Technology, Nanjing Agricultural University, Nanjing, 210095, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Hu
authors.affiliation: Key Laboratory of Synthetic Rubber & Laboratory of Advanced Power Sources, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China.
authors.forename: Fengchao
authors.initials: F
authors.lastname: Cui
authors.affiliation: College of Food Science and Technology, Nanjing Agricultural University, Nanjing, 210095, PR China.
authors.forename: Fangping
authors.initials: F
authors.lastname: Yin
authors.affiliation: College of Food Science and Technology, Nanjing Agricultural University, Nanjing, 210095, PR China.
authors.forename: Xiaoxiong
authors.initials: X
authors.lastname: Zeng
authors.affiliation: College of Food Science and Technology, Nanjing Agricultural University, Nanjing, 210095, PR China. Electronic address: sunyi01@njau.edu.cn.
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Key Laboratory of Synthetic Rubber & Laboratory of Advanced Power Sources, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China. Electronic address: yunqi@ciac.ac.cn.
authors.forename: Yunqi
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002384:Catalysis; D020134:Catalytic Domain; D006868:Hydrolysis; D007536:Isomerism; D007700:Kinetics; D008024:Ligands; D008049:Lipase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D011801:Quinic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013552:Swine
chemical_list: D008024:Ligands; C472707:caffeoylquinic acid; D011801:Quinic Acid; D008049:Lipase
keywords: Chlorogenic acids; Ligand–protein complex; Pancreatic lipase