1ycq

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(New page: 200px<br /> <applet load="1ycq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ycq, resolution 2.3&Aring;" /> '''XENOPUS LAEVIS MDM2 ...)
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[[Image:1ycq.gif|left|200px]]<br />
 
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<applet load="1ycq" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1ycq, resolution 2.3&Aring;" />
 
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'''XENOPUS LAEVIS MDM2 BOUND TO THE TRANSACTIVATION DOMAIN OF HUMAN P53'''<br />
 
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==Overview==
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==XENOPUS LAEVIS MDM2 BOUND TO THE TRANSACTIVATION DOMAIN OF HUMAN P53==
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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.
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<StructureSection load='1ycq' size='340' side='right'caption='[[1ycq]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1ycq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. The July 2002 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''p53 Tumor Suppressor'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2002_7 10.2210/rcsb_pdb/mom_2002_7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YCQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YCQ FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ycq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ycq OCA], [https://pdbe.org/1ycq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ycq RCSB], [https://www.ebi.ac.uk/pdbsum/1ycq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ycq ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/MDM2_XENLA MDM2_XENLA] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degration by the proteasome (By similarity).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/yc/1ycq_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ycq ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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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]]
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*[[MDM2|MDM2]]
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*[[MDM2 3D structures|MDM2 3D structures]]
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==About this Structure==
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*[[P53 3D structures|P53 3D structures]]
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1YCQ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. The following page contains interesting information on the relation of 1YCQ with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb31_1.html p53 Tumor Suppressor]]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1YCQ OCA].
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__TOC__
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</StructureSection>
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==Reference==
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[[Category: Homo sapiens]]
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8875929 8875929]
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[[Category: Large Structures]]
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[[Category: Protein complex]]
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[[Category: RCSB PDB Molecule of the Month]]
[[Category: Xenopus laevis]]
[[Category: Xenopus laevis]]
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[[Category: p53 Tumor Suppressor]]
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[[Category: P53 Tumor Suppressor]]
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[[Category: Kussie, P.H.]]
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[[Category: Kussie PH]]
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[[Category: Pavletich, N.P.]]
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[[Category: Pavletich NP]]
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[[Category: activator]]
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[[Category: anti-oncogene]]
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[[Category: complex (oncogene protein/peptide)]]
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[[Category: dna-binding]]
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[[Category: nuclear protein]]
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[[Category: phosphorylation]]
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[[Category: transcription regulation]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:18:02 2007''
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Current revision

XENOPUS LAEVIS MDM2 BOUND TO THE TRANSACTIVATION DOMAIN OF HUMAN P53

PDB ID 1ycq

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