Characterization of the class IIa histone deacetylases substrate specificity
Identifikátory výsledku
Kód výsledku v 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>
Výsledek na webu
<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>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Characterization of the class IIa histone deacetylases substrate specificity
Popis výsledku v původním jazyce
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.
Název v anglickém jazyce
Characterization of the class IIa histone deacetylases substrate specificity
Popis výsledku anglicky
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.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10602 - Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology
Návaznosti výsledku
Projekt
<a href="/cs/project/GA21-31806S" target="_blank" >GA21-31806S: Ovlivnění strukturních a funkčních charakteristik chaperonu HSP90 prostřednictvím reverzibilní acetylace</a><br>
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2022
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
FASEB Journal
ISSN
0892-6638
e-ISSN
1530-6860
Svazek periodika
36
Číslo periodika v rámci svazku
5
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
10
Strana od-do
e22287
Kód UT WoS článku
000778267400001
EID výsledku v databázi Scopus
2-s2.0-85127273793