Uncovering Robust Delactoylase and Depyruvoylase Activities of HDAC Isoforms

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F22%3A00558797" target="_blank" >RIV/86652036:_____/22:00558797 - isvavai.cz</a>

Výsledek na webu

<a href="https://pubs.acs.org/doi/10.1021/acschembio.1c00863" target="_blank" >https://pubs.acs.org/doi/10.1021/acschembio.1c00863</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acschembio.1c00863" target="_blank" >10.1021/acschembio.1c00863</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Uncovering Robust Delactoylase and Depyruvoylase Activities of HDAC Isoforms

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Uncovering Robust Delactoylase and Depyruvoylase Activities of HDAC Isoforms

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

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

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

ACS Chemical Biology

ISSN

1554-8929

e-ISSN

1554-8937

Svazek periodika

17

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

1364-1375

Kód UT WoS článku

000813511100001

EID výsledku v databázi Scopus

2-s2.0-85132223467