1dt7

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==Overview==
==Overview==
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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.
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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.
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==Disease==
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Known diseases associated with this structure: Adrenal cortical carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Breast cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Colorectal cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Hepatocellular carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Histiocytoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Li-Fraumeni syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Multiple malignancy syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Nasopharyngeal carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Osteosarcoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Pancreatic cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Thyroid carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]]
==About this Structure==
==About this Structure==
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[[Category: Protein complex]]
[[Category: Protein complex]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
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[[Category: Baldisseri, D.M.]]
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[[Category: Baldisseri, D M.]]
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[[Category: Rustandi, R.R.]]
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[[Category: Rustandi, R R.]]
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[[Category: Weber, D.J.]]
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[[Category: Weber, D J.]]
[[Category: CA]]
[[Category: CA]]
[[Category: c-terminal domain of p53]]
[[Category: c-terminal domain of p53]]
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[[Category: s100b]]
[[Category: s100b]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 13:42:03 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:20:11 2008''

Revision as of 10:20, 21 February 2008


1dt7

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SOLUTION STRUCTURE OF THE C-TERMINAL NEGATIVE REGULATORY DOMAIN OF P53 IN A COMPLEX WITH CA2+-BOUND S100B(BB)

Contents

Overview

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.

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

1DT7 is a Protein complex structure of sequences from Rattus norvegicus with as ligand. Full crystallographic information is available from OCA.

Reference

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

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