1ma3: Difference between revisions
New page: left|200px<br /> <applet load="1ma3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ma3, resolution 2.0Å" /> '''Structure of a Sir2 ... |
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[[Image:1ma3.gif|left|200px]]<br /> | [[Image:1ma3.gif|left|200px]]<br /><applet load="1ma3" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1ma3, resolution 2.0Å" /> | caption="1ma3, resolution 2.0Å" /> | ||
'''Structure of a Sir2 enzyme bound to an acetylated p53 peptide'''<br /> | '''Structure of a Sir2 enzyme bound to an acetylated p53 peptide'''<br /> | ||
==Overview== | ==Overview== | ||
Sir2 proteins are NAD(+)-dependent protein deacetylases that play key | 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. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1MA3 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Archaeoglobus_fulgidus Archaeoglobus fulgidus] with ZN and MES as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 1MA3 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Archaeoglobus_fulgidus Archaeoglobus fulgidus] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=MES:'>MES</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MA3 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Archaeoglobus fulgidus]] | [[Category: Archaeoglobus fulgidus]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Avalos, J | [[Category: Avalos, J L.]] | ||
[[Category: Boeke, J | [[Category: Boeke, J D.]] | ||
[[Category: Celic, I.]] | [[Category: Celic, I.]] | ||
[[Category: Cosgrove, M | [[Category: Cosgrove, M S.]] | ||
[[Category: Muhammad, S.]] | [[Category: Muhammad, S.]] | ||
[[Category: Wolberger, C.]] | [[Category: Wolberger, C.]] | ||
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[[Category: enzyme-substrate complex]] | [[Category: enzyme-substrate complex]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:53:06 2008'' | ||
Revision as of 14:53, 21 February 2008
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Structure of a Sir2 enzyme bound to an acetylated p53 peptide
OverviewOverview
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.
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
1MA3 is a Protein complex structure of sequences from Archaeoglobus fulgidus with and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
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:12408821
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