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The unraveling of substrate specificity of histone deacetylase 6 domains using acetylome peptide microarrays and peptide libraries
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SYSNO ASEP 0505012 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title The unraveling of substrate specificity of histone deacetylase 6 domains using acetylome peptide microarrays and peptide libraries Author(s) Kutil, Zsofia (BTO-N) RID, ORCID
Škultétyová, Ĺubica (BTO-N) RID
Rauh, D. (DE)
Meleshin, M. (DE)
Šnajdr, Ivan (UOCHB-X) ORCID
Nováková, Zora (BTO-N) ORCID, RID
Mikesova, Jana (BTO-N)
Pavlíček, Jiří (BTO-N) RID
Hadzima, Martin (UOCHB-X) ORCID
Baranová, Petra (BTO-N)
Havlínová, Barbora (BTO-N)
Majer, Pavel (UOCHB-X)
Schutkowski, M. (DE)
Bařinka, Cyril (BTO-N) RID, ORCIDNumber of authors 14 Source Title FASEB Journal. - : Wiley - ISSN 0892-6638
Roč. 33, č. 3 (2019), s. 4035-4045Number of pages 11 s. Language eng - English Country US - United States Keywords human acetylome ; deacylation ; deformylation Subject RIV EB - Genetics ; Molecular Biology OECD category Biochemistry and molecular biology Subject RIV - cooperation Institute of Organic Chemistry and Biochemistry - Genetics ; Molecular Biology R&D Projects GA15-19640S GA ČR - Czech Science Foundation (CSF) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support BTO-N - RVO:86652036 ; UOCHB-X - RVO:61388963 UT WOS 000459794800074 EID SCOPUS 85075552990 DOI 10.1096/fj.201801680R Annotation Histone deacetylase 6 (HDAC6) is a multidomain cytosolic hydrolase acting mostly on nonhistone protein substrates. Investigations of the substrate specificity of HDAC6 are confounded by the presence of 2 catalytically active deacetylase domains (DD1 and DD2). In this study, acetylome peptide microarrays and peptide libraries were used to map the substrate specificity of DD1 and DD2 of human HDAC6. The results show that DD1 is solely responsible for the deacetylation of substrates harboring the acetyllysine at their C terminus, whereas DD2 exclusively deacetylates peptides with an internal acetyllysine residue. Also, statistical analysis of the deacetylation data revealed amino acid preferences at individual positions flanking the acetyllysine, where glycine and arginine residues are favored at positions N-terminal to the central acetyllysine, negatively charged glutamate is strongly disfavored throughout the sequence. Finally, the deacylation activity of HDAC6 was profiled by using a panel of acyl derivatives of the optimized peptide substrate and showed that HDAC6 acts as a proficient deformylase. Our data thus offer a detailed insight into the substrate preferences of the individual HDAC6 domains at the peptide level, and these findings can in turn help in elucidating the biologic roles of the enzyme and facilitate the development of new domain-specific inhibitors as research tools or therapeutic agents.Kutil, Z., Skultetyova, L., Rauh, D., Meleshin, M., Snajdr, I., Novakova, Z., Mikesova, J., Pavlicek, J., Hadzima, M., Baranova, P., Havlinova, B., Majer, P., Schutkowski, M., Barinka, C. The unraveling of substrate specificity of histone deacetylase 6 domains using acetylome peptide microarrays and peptide libraries. Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2020 Electronic address https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.201801680R
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