This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1ycr
From Proteopedia
|
MDM2 BOUND TO THE TRANSACTIVATION DOMAIN OF P53
Contents |
Overview
The MDM2 oncoprotein is a cellular inhibitor of the p53 tumor suppressor, in that it can bind the transactivation domain of p53 and downregulate its, ability to activate transcription. In certain cancers, MDM2 amplification, is a common event and contributes to the inactivation of p53. The crystal, structure of the 109-residue amino-terminal domain of MDM2 bound to a, 15-residue transactivation domain peptide of p53 revealed that MDM2 has a, deep hydrophobic cleft on which the p53 peptide binds as an amphipathic, alpha helix. The interface relies on the steric complementarity between, the MDM2 cleft and the hydrophobic face of the p53 alpha helix and, in, particular, on a triad of p53 amino acids-Phe19, Trp23, and Leu26-which, insert deep into the MDM2 cleft. These same p53 residues are also involved, in transactivation, supporting the hypothesis that MDM2 inactivates p53 by, concealing its transactivation domain. The structure also suggests that, the amphipathic alpha helix may be a common structural motif in the, binding of a diverse family of transactivation factors to the TATA-binding, protein-associated factors.
Disease
Known diseases associated with this structure: Adrenal cortical carcinoma OMIM:[191170], Breast cancer OMIM:[191170], Colorectal cancer OMIM:[191170], Hepatocellular carcinoma OMIM:[191170], Histiocytoma OMIM:[191170], Li-Fraumeni syndrome OMIM:[191170], Multiple malignancy syndrome OMIM:[191170], Nasopharyngeal carcinoma OMIM:[191170], Osteosarcoma OMIM:[191170], Pancreatic cancer OMIM:[191170], Thyroid carcinoma OMIM:[191170]
About this Structure
1YCR is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain., Kussie PH, Gorina S, Marechal V, Elenbaas B, Moreau J, Levine AJ, Pavletich NP, Science. 1996 Nov 8;274(5289):948-53. PMID:8875929
Page seeded by OCA on Fri Feb 15 17:11:37 2008
