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- Title
Ser133 phosphate-KIX interactions in the CREB-CBP complex: an ab initio molecular dynamics study.
- Authors
Dal Peraro, Matteo; Alber, Frank; Carloni, Paolo
- Abstract
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.
- Subjects
CYCLIC adenylic acid; CARRIER proteins; BIOCHEMICAL mechanism of action
- Publication
European Biophysics Journal, 2001, Vol 30, Issue 1, p75
- ISSN
0175-7571
- Publication type
Article
- DOI
10.1007/s002490000112