8XE7

Crystal structure of human Sirt2 without Sirt2-specific insertion

8XE7 の概要

• エントリーDOI: 10.2210/pdb8xe7/pdb
• 分子名称: NAD-dependent protein deacetylase sirtuin-2, ZINC ION (3 entities in total)
• 機能のキーワード: deacetylation, zn binding protein, metal binding protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33306.69

構造登録者

Konuma, T.,Akashi, S. (登録日: 2023-12-11, 公開日: 2024-05-22)

主引用文献

Suzuki, N.,Konuma, T.,Ikegami, T.,Akashi, S.
Biophysical insights into the dimer formation of human Sirtuin 2.
Protein Sci., 33:e4994-e4994, 2024

PubMed Abstract: Sirtuin 2 (SIRT2) is a class III histone deacetylase that is highly conserved from bacteria to mammals. We prepared and characterized the wild-type (WT) and mutant forms of the histone deacetylase (HDAC) domain of human SIRT2 (hSIRT2) using various biophysical methods and evaluated their deacetylation activity. We found that WT hSIRT2 HDAC (residues 52-357) forms a homodimer in a concentration-dependent manner with a dimer-monomer dissociation constant of 8.3 ± 0.5 μM, which was determined by mass spectrometry. The dimer was disrupted into two monomers by binding to the HDAC inhibitors SirReal1 and SirReal2. We also confirmed dimer formation of hSIRT2 HDAC in living cells using a NanoLuc complementation reporter system. Examination of the relationship between dimer formation and deacetylation activity using several mutants of hSIRT2 HDAC revealed that some non-dimerizing mutants exhibited deacetylation activity for the N-terminal peptide of histone H3, similar to the wild type. The hSIRT2 HDAC mutant Δ292-306, which lacks a SIRT2-specific disordered loop region, was identified to exist as a monomer with slightly reduced deacetylation activity; the X-ray structure of the mutant Δ292-306 was almost identical to that of the WT hSIRT2 HDAC bound to an inhibitor. These results indicate that hSIRT2 HDAC forms a dimer, but this is independent of deacetylation activity. Herein, we discuss insights into the dimer formation of hSIRT2 based on our biophysical experimental results.

PubMed: 38647411
DOI: 10.1002/pro.4994

実験手法

X-RAY DIFFRACTION (1.95 Å)