Number of the records: 1
Uncovering Robust Delactoylase and Depyruvoylase Activities of HDAC Isoforms
- 1.
SYSNO ASEP 0558797 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Uncovering Robust Delactoylase and Depyruvoylase Activities of HDAC Isoforms Author(s) Zessin, M. (DE)
Meleshin, M. (DE)
Praetorius, L. (DE)
Sippl, W. (DE)
Bařinka, Cyril (BTO-N) RID, ORCID
Schutkowski, M. (DE)Number of authors 6 Source Title ACS Chemical Biology. - : American Chemical Society - ISSN 1554-8929
Roč. 17, č. 6 (2022), s. 1364-1375Number of pages 12 s. Language eng - English Country US - United States Keywords histone crotonylation ; lysine ; inhibitor ; substrate Subject RIV EB - Genetics ; Molecular Biology OECD category Biochemistry and molecular biology R&D Projects GA21-31806S GA ČR - Czech Science Foundation (CSF) Method of publishing Limited access Institutional support BTO-N - RVO:86652036 UT WOS 000813511100001 EID SCOPUS 85132223467 DOI 10.1021/acschembio.1c00863 Annotation Zinc-dependent histone deacetylases (HDACs) and sirtuins (SIRT) represent two different classes of enzymes which are responsible for deacylation of modified lysine side chains. The repertoire of acyl residues on lysine side chains identified in vivo is rapidly growing, and very recently lysine lactoylation was described to be involved in metabolic reprogramming. Additionally, lysine pyruvoylation represents a marker for aging and liver cirrhosis. Here, we report a systematic analysis of acyl-specificity of human zinc-dependent HDAC and sirtuin isoforms. We identified HDAC3 as a robust delactoylase with several-thousand-fold higher activity as compared to SIRT2, which was claimed to be the major in vivo delactoylase. Additionally, we systematically searched for enzymes, capable of removing pyruvoyl residues from lysine side chains. Using model peptides, we uncovered high depyruvoylase activity for HDAC6 and HDAC8. Interestingly, such substrates have extremely low K-M values for both HDAC isoforms, pointing to possible in vivo functions. Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2023 Electronic address https://pubs.acs.org/doi/10.1021/acschembio.1c00863
Number of the records: 1