3PDH

Structure of Sir2Tm bound to a propionylated peptide

3PDH の概要

• エントリーDOI: 10.2210/pdb3pdh/pdb
• 関連するPDBエントリー: 2H2D 2H2F 2H4F 2H4J
• 分子名称: NAD-dependent deacetylase, Cellular tumor antigen p53 18-residue peptide, ZINC ION, ... (4 entities in total)
• 機能のキーワード: rossmann fold, deacetylase, deacylase, depropionylase, n6-propionyl-lysine, hydrolase
• 由来する生物種: Thermotoga maritima; 詳細
• 細胞内の位置: Cytoplasm (Probable): Q9WYW0; Cytoplasm. Isoform 1: Nucleus. Isoform 2: Nucleus. Isoform 3: Nucleus. Isoform 4: Nucleus. Isoform 7: Nucleus. Isoform 8: Nucleus. Isoform 9: Cytoplasm: P04637
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29788.75

構造登録者

Wolberger, C.,Bheda, P. (登録日: 2010-10-22, 公開日: 2011-01-19, 最終更新日: 2023-09-06)

主引用文献

Bheda, P.,Wang, J.T.,Escalante-Semerena, J.C.,Wolberger, C.
Structure of Sir2Tm bound to a propionylated peptide.
Protein Sci., 20:131-139, 2011

PubMed Abstract: Lysine propionylation is a recently identified post-translational modification that has been observed in proteins such as p53 and histones and is thought to play a role similar to acetylation in modulating protein activity. Members of the sirtuin family of deacetylases have been shown to have depropionylation activity, although the way in which the sirtuin catalytic site accommodates the bulkier propionyl group is not clear. We have determined the 1.8 Å structure of a Thermotoga maritima sirtuin, Sir2Tm, bound to a propionylated peptide derived from p53. A comparison with the structure of Sir2Tm bound to an acetylated peptide shows that hydrophobic residues in the active site shift to accommodate the bulkier propionyl group. Isothermal titration calorimetry data show that Sir2Tm binds propionylated substrates more tightly than acetylated substrates, but kinetic assays reveal that the catalytic rate of Sir2Tm deacylation of propionyl-lysine is slightly reduced to acetyl-lysine. These results serve to broaden our understanding of the newly identified propionyl-lysine modification and the ability of sirtuins to depropionylate, as well as deacetylate, substrates.

PubMed: 21080423
DOI: 10.1002/pro.544

実験手法

X-RAY DIFFRACTION (1.8 Å)