Molecular Mechanism of the Interaction between MDM2 and p53 Export

@article{citeulike:6083593, abstract = {We have investigated the kinetic and thermodynamic basis of the p53–MDM2 interaction using a set of peptides based on residues 15–29 of p53. Wild-type p53 peptide bound MDM2 with a dissociation constant of 580 nM. Phosphorylation of S15 and S20 did not affect binding, but T18 phosphorylation weakened binding tenfold, indicating that phosphorylation of only T18 is responsible for abrogating p53–MDM2 binding. Truncation to residues 17–26 increased affinity 13-fold, but further truncation to 19–26 abolished binding. NMR studies of the binding of the p53-derived peptides revealed global conformational changes of the overall structure of MDM2, stretching far beyond the binding cleft, indicating significant changes in the domain dynamics of MDM2 upon ligand binding.}, author = {Schon, Oliver and Friedler, Assaf and Bycroft, Mark and Freund, Stefan M. V. and Fersht, Alan R.}, citeulike-article-id = {6083593}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/S0022-2836(02)00852-5}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S0022283602008525}, day = {25}, doi = {10.1016/S0022-2836(02)00852-5}, issn = {00222836}, journal = {Journal of Molecular Biology}, keywords = {p53}, month = {October}, number = {3}, pages = {491--501}, posted-at = {2009-11-08 01:55:20}, priority = {2}, title = {Molecular Mechanism of the Interaction between MDM2 and p53}, url = {http://dx.doi.org/10.1016/S0022-2836(02)00852-5}, volume = {323}, year = {2002} }

TY - JOUR ID - citeulike:6083593 L3 - citeulike-article-id:6083593 N2 - We have investigated the kinetic and thermodynamic basis of the p53–MDM2 interaction using a set of peptides based on residues 15–29 of p53. Wild-type p53 peptide bound MDM2 with a dissociation constant of 580 nM. Phosphorylation of S15 and S20 did not affect binding, but T18 phosphorylation weakened binding tenfold, indicating that phosphorylation of only T18 is responsible for abrogating p53–MDM2 binding. Truncation to residues 17–26 increased affinity 13-fold, but further truncation to 19–26 abolished binding. NMR studies of the binding of the p53-derived peptides revealed global conformational changes of the overall structure of MDM2, stretching far beyond the binding cleft, indicating significant changes in the domain dynamics of MDM2 upon ligand binding. IS - 3 JF - Journal of Molecular Biology SN - 00222836 EP - 501 TI - Molecular Mechanism of the Interaction between MDM2 and p53 VL - 323 SP - 491 KW - p53 AU - Schon, Oliver AU - Friedler, Assaf AU - Bycroft, Mark AU - Freund, Stefan AU - Fersht, Alan PY - 2002/10/25/ UR - http://dx.doi.org/10.1016/S0022-2836(02)00852-5 ER -