title: Recognition of LXXLL by ligand binding domain of the Farnesoid X receptor in molecular dynamics simulation.
abstract: The Farnesoid X receptor (FXR) has recently become a potential therapeutical target. The recruitment of coactivator protein (specified by LXXLL sequence) is the initial step in transcriptional activation of nuclear receptors (NRs). In this paper, the process of recognition of the LXXLL motif by the ligand binding domain (LBD) of FXR is observed in a 25 ns molecular dynamics simulation. The hydrophobic and hydrogen bonding interactions between the LBD and the coactivator are fully analyzed. This observation provides justification for the 'on deck' model proposed by Nettles and Greene. At last, insight to the protein-polypeptide interactions and protein conformational changes are discussed.
authors.affiliation: Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, P. R. China, 200032.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Xi-Cheng
authors.initials: XC
authors.lastname: Dong
authors.forename: Min-Bo
authors.initials: MB
authors.lastname: Chen
mesh_terms: D020816:Amino Acid Motifs; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation* / Q000379:methods*; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry*; D015195:Drug Design; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D008956:Models, Chemical; D008968:Molecular Conformation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry*; D013997:Time Factors; D014157:Transcription Factors / Q000737:chemistry*; D015533:Transcriptional Activation; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D004268:DNA-Binding Proteins; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated