title: Ser133 phosphate-KIX interactions in the CREB-CBP complex: an ab initio molecular dynamics study.
abstract: Cyclic AMP response element binding protein (CREB) is involved in activation of transcriptional DNA machinery by binding to the coactivator CREB-binding protein (CBP). The interactions between CREB serine phosphate (pSer133) and specific CBP residues (Tyr658 and Lys662) play a crucial role for the thermodynamic stability of the CREB-CBP complex. Here we use ab initio methods to investigate the dynamics and energetics of a relatively large, fully hydrated model complex representing pSer133 and its counterparts of the CBP domain. The calculations suggest that: (1) key contributions to the stabilization of the complex arise not only from electrostatics (as previously proposed) but also from a previously unrecognized "low-barrier hydrogen bond" between pSer133 and Lys662; (2) hydration plays a crucial role for the stabilization of the phosphate charge; (3) formation of the complex involves a significant degree of reorganization of the electronic charge density.
authors.forename: M
authors.initials: M
authors.lastname: Dal Peraro
authors.forename: F
authors.initials: F
authors.lastname: Alber
authors.forename: P
authors.initials: P
authors.lastname: Carloni
mesh_terms: D001665:Binding Sites; D050882:CREB-Binding Protein; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry* / Q000378:metabolism*; D006860:Hydrogen Bonding; D007700:Kinetics; D008239:Lysine; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D010768:Phosphoserine; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011789:Quantum Theory; D055672:Static Electricity; D013997:Time Factors; D015534:Trans-Activators / Q000737:chemistry* / Q000378:metabolism*; D014443:Tyrosine
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D010768:Phosphoserine; D014443:Tyrosine; D050882:CREB-Binding Protein; D008239:Lysine