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Protein and Peptide Letters 2020The semi-synthetic acetoxycoumarins are known to acetylate proteins using novel enzymatic Calreticulin Transacetylase (CRTAase) system in cells. However, the...
BACKGROUND
The semi-synthetic acetoxycoumarins are known to acetylate proteins using novel enzymatic Calreticulin Transacetylase (CRTAase) system in cells. However, the nonenzymatic protein acetylation by polyphenolic acetates is not known.
OBJECTIVE
To investigate the ability of 7-acetoxy-4-methyl coumarin (7-AMC) to acetylate proteins non-enzymatically in the test tube.
METHODS
We incubated 7-AMC with BSA and analyzed the protein acetylation using Western blot technique. Further, BSA induced biophysical changes in the spectroscopic properties of 7-AMC was analyzed using Fluorescence spectroscopy.
RESULTS
Using pan anti-acetyl lysine antibody, herein we demonstrate that 7-AMC acetylates Bovine Serum Albumin (BSA) in time and concentration dependent manner in the absence of any enzyme. 7-AMC is a relatively less fluorescent molecule compared to the parental compound, 7- hydroxy-4-methylcoumarin (7-HMC), however the fluorescence of 7-AMC increased by two fold on incubation with BSA, depending on the time of incubation and concentration of BSA. Analysis of the reaction mixture of 7-AMC and BSA after filtration revealed that the increased fluorescence is associated with the compound of lower molecular weight in the filtrate and not residual BSA, suggesting that the less fluorescent 7-AMC undergoes self-hydrolysis in the presence of protein to give highly fluorescent parental molecule 7-HMC and acetate ion in polar solvent (phosphate buffered saline, PBS). The protein augmented conversion of 7-AMC to 7-HMC was found to be linearly related to the protein concentration.
CONCLUSION
Thus protein acetylation induced by 7-AMC could also be non-enzymatic in nature and this molecule can be exploited for quantification of proteins.
Topics: Acetylation; Animals; Cattle; Coumarins; Serum Albumin, Bovine
PubMed: 32133945
DOI: 10.2174/0929866527666200305143016 -
FASEB Journal : Official Publication of... Nov 2019Impaired glycolysis has pathologic effects on the occurrence and progression of liver diseases, and it appears that glycolysis is increased to different degrees in... (Review)
Review
Impaired glycolysis has pathologic effects on the occurrence and progression of liver diseases, and it appears that glycolysis is increased to different degrees in different liver diseases. As an important post-translational modification, reversible lysine acetylation regulates almost all cellular processes, including glycolysis. Lysine acetylation can occur enzymatically with acetyltransferases or nonenzymatically with acetyl-coenzyme A. Accompanied by the progression of liver diseases, there seems to be a temporal and spatial variation between enzymatic and nonenzymatic acetylations in the regulation of glycolysis. Here, we summarize the most recent findings on the functions and targets of acetylation in controlling glycolysis in the different stages of liver diseases. In addition, we discuss the differences and causes between enzymatic and nonenzymatic acetylations in regulating glycolysis throughout the progression of liver diseases. Then, we review these new discoveries to provide the potential implications of these findings for therapeutic interventions in liver diseases.-Li, J., Wang, T., Xia, J., Yao, W., Huang, F. Enzymatic and nonenzymatic protein acetylations control glycolysis process in liver diseases.
Topics: Acetylation; Acetyltransferases; Escherichia coli Proteins; Glycolysis; Humans; Liver Diseases; Protein Processing, Post-Translational
PubMed: 31370704
DOI: 10.1096/fj.201901175R -
Leveraging Protein Dynamics to Identify Functional Phosphorylation Sites using Deep Learning Models.Journal of Chemical Information and... Jul 2022Accurate prediction of post-translational modifications (PTMs) is of great significance in understanding cellular processes, by modulating protein structure and... (Review)
Review
Accurate prediction of post-translational modifications (PTMs) is of great significance in understanding cellular processes, by modulating protein structure and dynamics. Nowadays, with the rapid growth of protein data at different "omics" levels, machine learning models largely enriched the prediction of PTMs. However, most machine learning models only rely on protein sequence and little structural information. The lack of the systematic dynamics analysis underlying PTMs largely limits the PTM functional predictions. In this research, we present two dynamics-centric deep learning models, namely, cDL-PAU and cDL-FuncPhos, by incorporating sequence, structure, and dynamics-based features to elucidate the molecular basis and underlying functional landscape of PTMs. cDL-PAU achieved satisfactory area under the curve (AUC) scores of 0.804-0.888 for predicting phosphorylation, acetylation, and ubiquitination (PAU) sites, while cDL-FuncPhos achieved an AUC value of 0.771 for predicting functional phosphorylation (FuncPhos) sites, displaying reliable improvements. Through a feature selection, the dynamics-based coupling and commute ability show large contributions in discovering PAU sites and FuncPhos sites, suggesting the allosteric propensity for important PTMs. The application of cDL-FuncPhos in three oncoproteins not only corroborates its strong performance in FuncPhos prioritization but also gains insight into the physical basis for the functions. The source code and data set of cDL-PAU and cDL-FuncPhos are available at https://github.com/ComputeSuda/PTM_ML.
Topics: Acetylation; Deep Learning; Phosphorylation; Protein Processing, Post-Translational; Proteins
PubMed: 35816597
DOI: 10.1021/acs.jcim.2c00484 -
Proteomics Jan 2016Post-translational modifications of proteins are key events in cellular metabolism and physiology regulation. Lysine acetylation is one of the best studied protein... (Review)
Review
Post-translational modifications of proteins are key events in cellular metabolism and physiology regulation. Lysine acetylation is one of the best studied protein modifications in eukaryotes, but, until recently, ignored in bacteria. However, proteomic advances have highlighted the diversity of bacterial lysine-acetylated proteins. The current data support the implication of lysine acetylation in various metabolic pathways, adaptation and virulence. In this review, we present a broad overview of the current knowledge of lysine acetylation in bacteria. We emphasize particularly the significant contribution of proteomics in this field.
Topics: Acetylation; Bacteria; Bacterial Proteins; Humans; Lysine; Metabolic Networks and Pathways; Protein Processing, Post-Translational; Proteomics
PubMed: 26390373
DOI: 10.1002/pmic.201500258 -
Plant Communications Jan 2022Lysine acetylation (LysAc) is a conserved and important post-translational modification (PTM) that plays a key role in plant physiological and metabolic processes. Based... (Review)
Review
Lysine acetylation (LysAc) is a conserved and important post-translational modification (PTM) that plays a key role in plant physiological and metabolic processes. Based on advances in Lys-acetylated protein immunoenrichment and mass-spectrometric technology, LysAc proteomics studies have been performed in many species. Such studies have made substantial contributions to our understanding of plant LysAc, revealing that Lys-acetylated histones and nonhistones are involved in a broad spectrum of plant cellular processes. Here, we present an extensive overview of recent research on plant Lys-acetylproteomes. We provide in-depth insights into the characteristics of plant LysAc modifications and the mechanisms by which LysAc participates in cellular processes and regulates metabolism and physiology during plant growth and development. First, we summarize the characteristics of LysAc, including the properties of Lys-acetylated sites, the motifs that flank Lys-acetylated lysines, and the dynamic alterations in LysAc among different tissues and developmental stages. We also outline a map of Lys-acetylated proteins in the Calvin-Benson cycle and central carbon metabolism-related pathways. We then introduce some examples of the regulation of plant growth, development, and biotic and abiotic stress responses by LysAc. We discuss the interaction between LysAc and N-terminal acetylation and the crosstalk between LysAc and other PTMs, including phosphorylation and succinylation. Finally, we propose recommendations for future studies in the field. We conclude that LysAc of proteins plays an important role in the regulation of the plant life cycle.
Topics: Acetylation; Lysine; Plant Proteins; Protein Processing, Post-Translational; Proteome
PubMed: 35059632
DOI: 10.1016/j.xplc.2021.100266 -
Nature Communications Dec 2023Acetylation of histones is a key post-translational modification that guides gene expression regulation. In yeast, the class I histone deacetylase containing Rpd3S...
Acetylation of histones is a key post-translational modification that guides gene expression regulation. In yeast, the class I histone deacetylase containing Rpd3S complex plays a critical role in the suppression of spurious transcription by removing histone acetylation from actively transcribed genes. The S. cerevisiae Rpd3S complex has five subunits (Rpd3, Sin3, Rco1, Eaf3, and Ume1) but its subunit stoichiometry and how the complex engages nucleosomes to achieve substrate specificity remains elusive. Here we report the cryo-EM structure of the complete Rpd3S complex bound to a nucleosome. Sin3 and two copies of subunits Rco1 and Eaf3 encircle the deacetylase subunit Rpd3 and coordinate the positioning of Ume1. The Rpd3S complex binds both trimethylated H3 tails at position lysine 36 and makes multiple additional contacts with the nucleosomal DNA and the H2A-H2B acidic patch. Direct regulation via the Sin3 subunit coordinates binding of the acetylated histone substrate to achieve substrate specificity.
Topics: Nucleosomes; Saccharomyces cerevisiae; Histones; Saccharomyces cerevisiae Proteins; Methylation; Acetylation; Acetyltransferases
PubMed: 38065958
DOI: 10.1038/s41467-023-43968-8 -
Biochemical Society Transactions Aug 2014Protein acetylation has emerged as a prominent post-translational modification that can occur on a wide variety of proteins. The metabolite acetyl-CoA is a key... (Review)
Review
Protein acetylation has emerged as a prominent post-translational modification that can occur on a wide variety of proteins. The metabolite acetyl-CoA is a key intermediate in energy metabolism that also serves as the acetyl group donor in protein acetylation modifications. Therefore such acetylation modifications might be coupled to the intracellular availability of acetyl-CoA. In the present article, we summarize recent evidence suggesting that the particular protein acetylation modifications enable the regulation of protein function in tune with acetyl-CoA availability and thus the metabolic state of the cell.
Topics: Acetyl Coenzyme A; Acetylation; Animals; Epigenesis, Genetic; Humans; Protein Processing, Post-Translational; Proteins
PubMed: 25109999
DOI: 10.1042/BST20140135 -
Journal of Agricultural and Food... Jul 2020Preslaughter handling has been shown to significantly affect meat quality, but the mechanisms are not fully understood. In this study, we investigated protein...
Preslaughter handling has been shown to significantly affect meat quality, but the mechanisms are not fully understood. In this study, we investigated protein phosphorylation and acetylation in pig muscles at early postmortem time and their associations with meat quality attributes. Thirty pigs were randomly assigned to traditional (TH, = 15) or mild handling (MH, = 15). Compared with TH, MH reduced the incidence of pale, soft, and exudative (PSE) or dark, firm, and dry (DFD) pork. MH induced 65 and 20 peptides that match with 39 and 12 proteins to be more highly phosphorylated and acetylated, respectively. Creatine kinase, β-enolase, α-1,4-glucan phosphorylase, tropomyosin, and myosin heavy chain isoforms 1, 4, and 7 were found to be simultaneously phosphorylated and acetylated, which may involve glycolysis, tight junctions, and muscle contraction. The phosphorylation and acetylation levels of differential proteins showed significant correlations with meat quality traits. These findings indicate that preslaughter MH can improve meat quality by regulating protein phosphorylation and acetylation involving energy metabolism in muscle.
Topics: Acetylation; Animals; Energy Metabolism; Female; Male; Meat; Muscle Proteins; Muscle, Skeletal; Peptides; Phosphorylation; Swine
PubMed: 32543862
DOI: 10.1021/acs.jafc.0c01822 -
Advanced Science (Weinheim,... Aug 2023Male-specific lethal 1 (MSL1) is critical for the formation of MSL histone acetyltransferase complex which acetylates histone H4 Lys16 (H4K16ac) to activate gene...
Male-specific lethal 1 (MSL1) is critical for the formation of MSL histone acetyltransferase complex which acetylates histone H4 Lys16 (H4K16ac) to activate gene expression. However, the role of MSL1 in liver regeneration is poorly understood. Here, this work identifies MSL1 as a key regulator of STAT3 and histone H4 (H4) in hepatocytes. MSL1 forms condensates with STAT3 or H4 through liquid-liquid phase separation to enrich acetyl-coenzyme A (Ac-CoA), and Ac-CoA in turn enhances MSL1 condensate formation, synergetically promoting the acetylation of STAT3 K685 and H4K16, thus stimulating liver regeneration after partial hepatectomy (PH). Additionally, increasing Ac-CoA level can enhance STAT3 and H4 acetylation, thus promoting liver regeneration in aged mice. The results demonstrate that MSL1 condensate-mediated STAT3 and H4 acetylation play an important role in liver regeneration. Thus, promoting the phase separation of MSL1 and increasing Ac-CoA level may be a novel therapeutic strategy for acute liver diseases and transplantation.
Topics: Male; Mice; Animals; Histones; Acetylation; Liver Regeneration; Cell Nucleus
PubMed: 37279389
DOI: 10.1002/advs.202301094 -
Spectrochimica Acta. Part A, Molecular... Oct 2022Acetylation is a common and extremely important protein modification in biology, referring to the covalent attachment of an acetyl group to the amino group. There are...
Acetylation is a common and extremely important protein modification in biology, referring to the covalent attachment of an acetyl group to the amino group. There are two forms of protein acetylation, which are lysine Nε-acetylation and N-terminal Nα-acetylation, respectively. Protein lysine Nε-acetylation is a globally important post-translational modification which plays a critical regulatory role in almost all aspects of cell metabolism. In addition, whether lysine on the N-terminal of protein can undergo Nα-acetylation is still a controversial viewpoint. Carrying out further molecular study of the role of acetylation is also the one of challenges. In order to investigate the protein acetylation more effectively, it is thus necessary to have a thorough and comprehensive understanding of lysine acetylation. In this work, both Raman and infrared (IR) spectra of L-lysine Nε-Ace-Lys, Nα-Ace-Lys, and NαNε-Ace-Lys were explored through both experimental experiment and theoretical computation based on density function theory (DFT). Vibration assignments and geometry structures of three acetylated lysines were therefore obtained for the first time in this work. The IR or Raman spectra of four molecules are very different from each other, which can be easily distinguished from the characteristic bands at 1500-1700 cm and 3200-3400 cm regions. Therefore, this work may provide the guide for probing the protein acetylation by Raman and IR spectroscopy.
Topics: Acetylation; Lysine; Protein Processing, Post-Translational; Spectrum Analysis, Raman; Vibration
PubMed: 35594700
DOI: 10.1016/j.saa.2022.121371