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1ma3

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[[Image:1ma3.gif|left|200px]]
 
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{{Structure
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==Structure of a Sir2 enzyme bound to an acetylated p53 peptide==
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|PDB= 1ma3 |SIZE=350|CAPTION= <scene name='initialview01'>1ma3</scene>, resolution 2.0&Aring;
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<StructureSection load='1ma3' size='340' side='right'caption='[[1ma3]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC ACID'>MES</scene>
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<table><tr><td colspan='2'>[[1ma3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Archaeoglobus_fulgidus Archaeoglobus fulgidus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MA3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MA3 FirstGlance]. <br>
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|ACTIVITY=
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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&#8491;</td></tr>
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|GENE= SIR2-Af2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2234 Archaeoglobus fulgidus])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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}}
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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=1ma3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ma3 OCA], [https://pdbe.org/1ma3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ma3 RCSB], [https://www.ebi.ac.uk/pdbsum/1ma3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ma3 ProSAT]</span></td></tr>
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</table>
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'''Structure of a Sir2 enzyme bound to an acetylated p53 peptide'''
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== Function ==
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[https://www.uniprot.org/uniprot/NPD2_ARCFU NPD2_ARCFU] NAD-dependent protein deacetylase which modulates the activities of several enzymes which are inactive in their acetylated form. Deacetylates the N-terminal lysine residue of Alba, the major archaeal chromatin protein and that, in turn, increases Alba's DNA binding affinity, thereby repressing transcription (By similarity).[HAMAP-Rule:MF_01121]
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== Evolutionary Conservation ==
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==Overview==
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[[Image:Consurf_key_small.gif|200px|right]]
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Sir2 proteins are NAD(+)-dependent protein deacetylases that play key roles in transcriptional regulation, DNA repair, and life span regulation. The structure of an archaeal Sir2 enzyme, Sir2-Af2, bound to an acetylated p53 peptide reveals that the substrate binds in a cleft in the enzyme, forming an enzyme-substrate beta sheet with two flanking strands in Sir2-Af2. The acetyl-lysine inserts into a conserved hydrophobic tunnel that contains the active site histidine. Comparison with other structures of Sir2 enzymes suggests that the apoenzyme undergoes a conformational change upon substrate binding. Based on the Sir2-Af2 substrate complex structure, mutations were made in the other A. fulgidus sirtuin, Sir2-Af1, that increased its affinity for the p53 peptide.
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Check<jmol>
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<jmolCheckbox>
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==Disease==
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ma/1ma3_consurf.spt"</scriptWhenChecked>
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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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<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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==About this Structure==
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</jmolCheckbox>
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1MA3 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Archaeoglobus_fulgidus Archaeoglobus fulgidus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MA3 OCA].
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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=1ma3 ConSurf].
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<div style="clear:both"></div>
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==Reference==
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__TOC__
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Structure of a Sir2 enzyme bound to an acetylated p53 peptide., Avalos JL, Celic I, Muhammad S, Cosgrove MS, Boeke JD, Wolberger C, Mol Cell. 2002 Sep;10(3):523-35. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12408821 12408821]
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</StructureSection>
[[Category: Archaeoglobus fulgidus]]
[[Category: Archaeoglobus fulgidus]]
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[[Category: Protein complex]]
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[[Category: Homo sapiens]]
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[[Category: Avalos, J L.]]
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[[Category: Large Structures]]
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[[Category: Boeke, J D.]]
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[[Category: Avalos JL]]
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[[Category: Celic, I.]]
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[[Category: Boeke JD]]
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[[Category: Cosgrove, M S.]]
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[[Category: Celic I]]
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[[Category: Muhammad, S.]]
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[[Category: Cosgrove MS]]
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[[Category: Wolberger, C.]]
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[[Category: Muhammad S]]
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[[Category: MES]]
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[[Category: Wolberger C]]
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[[Category: ZN]]
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[[Category: enzyme-substrate complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:40:53 2008''
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Current revision

Structure of a Sir2 enzyme bound to an acetylated p53 peptide

PDB ID 1ma3

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