Uncovering Robust Delactoylase and Depyruvoylase Activities of HDAC Isoforms.

ACS Chem Biol

Department of Enzymology, Charles Tanford Protein Center, Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, Halle/Saale, 06120, Germany.

Published: June 2022

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 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 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 values for both HDAC isoforms, pointing to possible functions.

Download full-text PDF

Source
http://dx.doi.org/10.1021/acschembio.1c00863DOI Listing

Publication Analysis

Top Keywords

lysine side
12
side chains
12
robust delactoylase
8
hdac isoforms
8
residues lysine
8
lysine
5
uncovering robust
4
delactoylase depyruvoylase
4
depyruvoylase activities
4
activities hdac
4

Similar Publications

Riboflavin-mediated ultraviolet photosensitive oxidation of beef myofibrillar proteins with different storage times.

Food Chem

January 2025

Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences/Key Laboratory of Agricultural Product Processing, Ministry of Agriculture, Beijing 100193, China; Zibo Institute for Digital Agriculture and Rural Research, Zibo 255051, China. Electronic address:

The study was designed to investigate the mechanism of Riboflavin (RF)-mediated UVA photosensitive oxidation on beef myofibrillar proteins (MP) oxidized at different storage times. To elucidate the direct relationship between RF and protein oxidation, the mechanism of action was analyzed in terms of amino acid and side chain residues, protein structure, and protein oxidative metabolism. Oxidation of MP resulted in significant changes in the levels of carbonyls, sulfhydryls, Lysine, Arginine, Threonin, and Histidine.

View Article and Find Full Text PDF

In this article, we report on the alginate heterografted by Poly(N-isopropyl acrylamide-co-N-tert-butyl acrylamide) and Poly(N-isopropyl acrylamide) (ALG-g-P(NIPAM86-co-NtBAM14)-g-PNIPAM) copolymer thermoresponsive hydrogel, reinforced by substituting part of the 5 wt% aqueous formulation by small amounts of Poly(acrylic acid)-g-P(boc-L-Lysine) (PAA-g-P(b-LL)) graft copolymer (up to 1 wt%). The resulting complex hydrogels were explored by oscillatory and steady-state shear rheology. The thermoresponsive profile of the formulations were affected remarkably by increasing the PAA-g-P(b-LL) component of the polymer blend.

View Article and Find Full Text PDF

In the face of rising the threat of resistant pathogens, antimicrobial peptides (AMPs) offer a viable alternative to the current challenge due to their broad-spectrum activity. This study focuses on enhancing the efficacy of temporin-SHa derived NST-2 peptide (), which is known for its antimicrobial and anticancer activities. We synthesized new analogs of using three strategies, i.

View Article and Find Full Text PDF
Article Synopsis
  • The rise of multidrug-resistant bacteria highlights the urgent need for new antimicrobial medicines, leading to the investigation of antimicrobial peptoids as potential alternatives.
  • Thirteen peptoid analogues were synthesized with varying alkyl side chains to analyze their antibacterial properties, and only one, called Tosyl-Octyl-Peptoid (TOP), showed significant broad-spectrum bactericidal activity.
  • TOP effectively kills bacteria in both dividing and non-dividing states, demonstrating promising minimum inhibitory concentrations and a high selectivity ratio, suggesting its potential as a future therapeutic option against resistant infections.
View Article and Find Full Text PDF

Selective labeling of tyrosine residues in proteins: insights from PTAD labeling and tandem mass spectrometry analysis.

Mol Omics

December 2024

Department of Chemistry and Biochemistry, University of Texas at Arlington, Box 19065, 700 Planetarium Place, Room 130, Arlington, TX 76019, USA.

Designing reagents for protein labeling is crucial for investigating cellular events and developing new therapeutics. Historically, much effort has been focused on labeling lysine and arginine residues due to their abundance on the protein periphery. The chemo-selectivity of these reagents is a challenging yet crucial parameter for deciphering properties specifically associated with the targeted amino acid.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!