Characterization of the class IIa histone deacetylases substrate specificity

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F22%3A00556614" target="_blank" >RIV/86652036:_____/22:00556614 - isvavai.cz</a>
Result on the web
<a href="https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202101663R" target="_blank" >https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202101663R</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1096/fj.202101663R" target="_blank" >10.1096/fj.202101663R</a>

Result language
angličtina
Original language name
Characterization of the class IIa histone deacetylases substrate specificity
Original language description
Class IIa histone deacetylases (HDACs) play critical roles in vertebrate development and physiology, yet direct evidence of their intrinsic deacetylase activity and on substrate specificity regarding the peptide sequence is still missing. In this study, we designed and synthesized a combinatorial peptide library allowing us to profile class IIa HDACs sequence specificity at positions +3 through3 from the central lysine modified by the well-accepted trifluoroacetyl function. Our data revealed a strong preference for bulky aromatic acids directly flanking the central trifluoroacetyllysine, while all class IIa HDACs disfavor positively charged residues and proline at the +1/-1 positions. The chemical nature of amino acid residues N-terminally to the central trifluoroacetyllysine has a more profound effect on substrate recognition as compared to residues located C-terminally. These findings were validated by designing selected favored and disfavored peptide sequences, with the favored ones are accepted with catalytic efficacy of 75 000 and 525 000 M-1 s(-1) for HDAC7 and HDAC5, respectively. Results reported here could help in developing class IIa HDACs inhibitors and also in the search for new natural class IIa HDACs substrates.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10602 - Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology

Project
<a href="/en/project/GA21-31806S" target="_blank" >GA21-31806S: Modulation of structural and functional properties of the HSP90 chaperone machinery by reversible acetylation</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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