8HLY

Crystal structure of SIRT3 in complex with H3K23la peptide

8HLY の概要

• エントリーDOI: 10.2210/pdb8hly/pdb
• 分子名称: NAD-dependent protein deacetylase sirtuin-3, mitochondrial, H3K23la peptide, GLYCEROL, ... (7 entities in total)
• 機能のキーワード: sirt3, lysine lactylation eraser, hydrolase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 32365.57

構造登録者

Zhuming, F.,Hao, Q. (登録日: 2022-12-01, 公開日: 2023-09-27, 最終更新日: 2023-11-15)

主引用文献

Fan, Z.,Liu, Z.,Zhang, N.,Wei, W.,Cheng, K.,Sun, H.,Hao, Q.
Identification of SIRT3 as an eraser of H4K16la.
Iscience, 26:107757-107757, 2023

PubMed Abstract: Lysine lactylation (Kla) is a novel histone post-translational modification discovered in late 2019. Later, HDAC1-3, were identified as the robust Kla erasers. While the Sirtuin family proteins showed weak eraser activities toward Kla, as reported. However, the catalytic mechanisms and physiological functions of HDACs and Sirtuins are not identical. In this study, we observed that SIRT3 exhibits a higher eraser activity against the H4K16la site than the other human Sirtuins. Crystal structures revealed the detailed binding mechanisms between lactyl-lysine peptides and SIRT3. Furthermore, a chemical probe, p-H4K16laAlk, was developed to capture potential Kla erasers from cell lysates. SIRT3 was captured by this probe and detected via proteomic analysis. And another chemical probe, p-H4K16la-NBD, was developed to detect the eraser-Kla delactylation processes directly via fluorescence indication. Our findings and chemical probes provide new directions for further investigating Kla and its roles in gene transcription regulation.

PubMed: 37720100
DOI: 10.1016/j.isci.2023.107757

実験手法

X-RAY DIFFRACTION (2 Å)