1ma3
From Proteopedia
| |||||||
| , resolution 2.0Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | SIR2-Af2 (Archaeoglobus fulgidus) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of a Sir2 enzyme bound to an acetylated p53 peptide
Contents |
Overview
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
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
1MA3 is a Protein complex structure of sequences from Archaeoglobus fulgidus. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Mar 20 12:40:53 2008
