title: Interaction between Pin1 and its natural product inhibitor epigallocatechin-3-gallate by spectroscopy and molecular dynamics simulations.
abstract: The binding of epigallocatechin-3-gallate (EGCG) to wild type Pin1 in solution was studied by spectroscopic methods and molecular dynamics simulations in this research to explore the binding mode and inhibition mechanism. The binding constants and number of binding sites per Pin1 for EGCG were calculated through the Stern-Volmer equation. The values of binding free energy and thermodynamic parameters were calculated and indicated that hydrogen bonds, electrostatic interaction and Van der Waals interaction played the major role in the binding process. The alterations of Pin1 secondary structure in the presence of EGCG were confirmed by far-UV circular dichroism spectra. The binding model at atomic-level revealed that EGCG was bound to the Glu12, Lys13, Arg14, Met15 and Arg17 in WW domain. Furthermore, EGCG could also interact with Arg69, Asp112, Cys113 and Ser114 in PPIase domain.
authors.affiliation: Key Laboratory of Bio-resources and Eco-environment of the Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610064, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xi
authors.affiliation: Key Laboratory of Bio-resources and Eco-environment of the Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610064, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Bio-resources and Eco-environment of the Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610064, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: He
authors.affiliation: Key Laboratory of Bio-resources and Eco-environment of the Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610064, PR China.
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Bio-resources and Eco-environment of the Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610064, PR China. Electronic address: dulinfang@scu.edu.cn.
authors.forename: Linfang
authors.initials: L
authors.lastname: Du
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001665:Binding Sites; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D000072340:NIMA-Interacting Peptidylprolyl Isomerase / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects; D013050:Spectrometry, Fluorescence; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D002392:Catechin; C045651:epigallocatechin gallate; C000606846:PIN1 protein, human
keywords: Epigallocatechin-3-gallate; Far-UV circular dichroism spectrum; Fluorescence spectroscopy; Molecular dynamics simulations; Pin 1