1MA3

Structure of a Sir2 enzyme bound to an acetylated p53 peptide

Summary for 1MA3

• Entry DOI: 10.2210/pdb1ma3/pdb
• Descriptor: Transcriptional regulatory protein, Sir2 family, Cellular tumor antigen p53, ZINC ION, ... (5 entities in total)
• Functional Keywords: enzyme-substrate complex, protein binding, transcription
• Biological source: Archaeoglobus fulgidus; More
• Cellular location: Cytoplasm (Probable): O30124; Cytoplasm. Isoform 1: Nucleus. Isoform 2: Nucleus. Isoform 3: Nucleus. Isoform 4: Nucleus. Isoform 7: Nucleus. Isoform 8: Nucleus. Isoform 9: Cytoplasm: P04637
• Total number of polymer chains: 2
• Total formula weight: 30937.17

Authors

Avalos, J.L.,Celic, I.,Muhammad, S.,Cosgrove, M.S.,Boeke, J.D.,Wolberger, C. (deposition date: 2002-07-31, release date: 2002-10-16, Last modification date: 2011-07-13)

Primary citation

Avalos, J.L.,Celic, I.,Muhammad, S.,Cosgrove, M.S.,Boeke, J.D.,Wolberger, C.
Structure of a Sir2 enzyme bound to an acetylated p53 peptide
Mol.Cell, 10:523-535, 2002

PubMed Abstract: 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.

PubMed: 12408821
DOI: 10.1016/S1097-2765(02)00628-7

Experimental method

X-RAY DIFFRACTION (2 Å)