1dt7
SOLUTION STRUCTURE OF THE C-TERMINAL NEGATIVE REGULATORY DOMAIN OF P53 IN A COMPLEX WITH CA2+-BOUND S100B(BB)
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OverviewOverview
A Ca2+ dependent conformational change in dimeric S100B(betabeta) is required for it to bind p53 and inhibit phosphorylation of this tumor suppressor in its C-terminal negative regulatory domain. A peptide derived from this region of p53 (residues 367-388) was found to have no regular structure in its native form by NMR spectroscopy, but becomes helical when bound to Ca2+ loaded S100B(betabeta). The three-dimensional structure of this complex reveals several favorable hydrophobic and electrostatic interactions between S100B(betabeta) and the p53 peptide in the binding pocket, where S100B(betabeta) sterically blocks sites of phosphorylation and acetylation on p53 that are important for transcription activation.
DiseaseDisease
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 StructureAbout this Structure
1DT7 is a Protein complex structure of sequences from Rattus norvegicus with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Structure of the negative regulatory domain of p53 bound to S100B(betabeta)., Rustandi RR, Baldisseri DM, Weber DJ, Nat Struct Biol. 2000 Jul;7(7):570-4. PMID:10876243
Page seeded by OCA on Thu Feb 21 12:20:11 2008