8HN9

Human SIRT3 Recognizing CCNE2K348la peptide

8HN9 の概要

• エントリーDOI: 10.2210/pdb8hn9/pdb
• 分子名称: NAD-dependent protein deacetylase sirtuin-3, mitochondrial, CCNE2 peptide, ZINC ION, ... (4 entities in total)
• 機能のキーワード: lyase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 62967.52

構造登録者

Wang, Y.,Ding, W. (登録日: 2022-12-07, 公開日: 2023-05-10, 最終更新日: 2023-11-15)

主引用文献

Jin, J.,Bai, L.,Wang, D.,Ding, W.,Cao, Z.,Yan, P.,Li, Y.,Xi, L.,Wang, Y.,Zheng, X.,Wei, H.,Ding, C.,Wang, Y.
SIRT3-dependent delactylation of cyclin E2 prevents hepatocellular carcinoma growth.
Embo Rep., 24:e56052-e56052, 2023

PubMed Abstract: Lysine lactylation (Kla) is a recently discovered histone mark derived from metabolic lactate. The NAD -dependent deacetylase SIRT3, which can also catalyze removal of the lactyl moiety from lysine, is expressed at low levels in hepatocellular carcinoma (HCC) and has been suggested to be an HCC tumor suppressor. Here we report that SIRT3 can delactylate non-histone proteins and suppress HCC development. Using SILAC-based quantitative proteomics, we identify cyclin E2 (CCNE2) as one of the lactylated substrates of SIRT3 in HCC cells. Furthermore, our crystallographic study elucidates the mechanism of CCNE2 K348la delactylation by SIRT3. Our results further suggest that lactylated CCNE2 promotes HCC cell growth, while SIRT3 activation by Honokiol induces HCC cell apoptosis and prevents HCC outgrowth in vivo by regulating Kla levels of CCNE2. Together, our results establish a physiological function of SIRT3 as a delactylase that is important for suppressing HCC, and our structural data could be useful for the future design of activators.

PubMed: 36896611
DOI: 10.15252/embr.202256052

実験手法

X-RAY DIFFRACTION (3.7 Å)