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Structure of a Sir2 enzyme bound to an acetylated p53 peptide

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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 with ZN and MES as ligands. 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

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