-
Molecules (Basel, Switzerland) Jul 2021The nature-identical engineered polysaccharide α-(1,3) glucan, produced by the enzymatic polymerization of sucrose, was chemically modified by acylation with succinic...
The nature-identical engineered polysaccharide α-(1,3) glucan, produced by the enzymatic polymerization of sucrose, was chemically modified by acylation with succinic anhydride. This modification reaction was initially performed at the micro scale in a TGA reactor to access a range of reaction conditions and to study the mechanism of the reaction. Subsequently, the best performing conditions were reproduced at the larger laboratory scale. The reaction products were characterized via coupled TGA/DSC analysis, FT-IR spectroscopy, solution viscosity and pH determination. The acylation path resulted in partially modifying the polysaccharide by altering its behavior in terms of thermal properties and solubility. The acylation in a solvent-free approach was found promising for the development of novel, potentially melt-processable and fully bio-based and biodegradable ester compounds.
Topics: Acylation; Glucans; Hydrogen-Ion Concentration; Polymerization; Succinic Anhydrides; Sucrose; Viscosity
PubMed: 34279397
DOI: 10.3390/molecules26134058 -
Trends in Biochemical Sciences Sep 2020Many chromatin-modifying enzymes require metabolic cofactors to support their catalytic activities, providing a direct path for fluctuations in metabolite availability... (Review)
Review
Many chromatin-modifying enzymes require metabolic cofactors to support their catalytic activities, providing a direct path for fluctuations in metabolite availability to regulate the epigenome. Over the past decade, our knowledge of this link has grown significantly. What began with studies showing that cofactor availability drives global abundances of chromatin modifications has transitioned to discoveries highlighting metabolic enzymes as loci-specific regulators of gene expression. Here, we cover our current understanding of mechanisms that facilitate the dynamic and complex relationship between metabolism and the epigenome, focusing on the roles of essential metabolic and chromatin associated enzymes. We discuss physiological conditions where availability of these epimetabolites is dynamically altered, highlighting known links to the epigenome and proposing other plausible connections.
Topics: Acetylation; Chromatin; DNA Methylation; Epigenome
PubMed: 32387193
DOI: 10.1016/j.tibs.2020.04.002 -
Journal of Proteome Research Jan 2021Protein -acylation (commonly known as palmitoylation) is a widespread reversible lipid modification, which plays critical roles in regulating protein localization,... (Review)
Review
Protein -acylation (commonly known as palmitoylation) is a widespread reversible lipid modification, which plays critical roles in regulating protein localization, activity, stability, and complex formation. The deregulation of protein -acylation contributes to many diseases such as cancer and neurodegenerative disorders. The past decade has witnessed substantial progress in proteomic analysis of protein -acylation, which significantly advanced our understanding of -acylation biology. In this review, we summarized the techniques for the enrichment of -acylated proteins or peptides, critically reviewed proteomic studies of protein -acylation at eight different levels, and proposed major challenges for the -acylproteomics field. In summary, proteome-scale analysis of protein -acylation comes of age and will play increasingly important roles in discovering new disease mechanisms, biomarkers, and therapeutic targets.
Topics: Acylation; Lipoylation; Protein S; Proteome; Proteomics
PubMed: 33253586
DOI: 10.1021/acs.jproteome.0c00409 -
Cells Feb 2022Adult hippocampal neurogenesis-the generation of new functional neurones in the adult brain-is impaired in aging and many neurodegenerative disorders. We recently showed... (Review)
Review
Adult hippocampal neurogenesis-the generation of new functional neurones in the adult brain-is impaired in aging and many neurodegenerative disorders. We recently showed that the acylated version of the gut hormone ghrelin (acyl-ghrelin) stimulates adult hippocampal neurogenesis while the unacylated form of ghrelin inhibits it, thus demonstrating a previously unknown function of unacyl-ghrelin in modulating hippocampal plasticity. Analysis of plasma samples from Parkinson's disease patients with dementia demonstrated a reduced acyl-ghrelin:unacyl-ghrelin ratio compared to both healthy controls and cognitively intact Parkinson's disease patients. These data, from mouse and human studies, suggest that restoring acyl-ghrelin signalling may promote the activation of pathways to support memory function. In this short review, we discuss the evidence for ghrelin's role in regulating adult hippocampal neurogenesis and the enzymes involved in ghrelin acylation and de-acylation as targets to treat mood-related disorders and dementia.
Topics: Acylation; Animals; Dementia; Ghrelin; Hippocampus; Humans; Mice; Neurogenesis; Parkinson Disease
PubMed: 35269387
DOI: 10.3390/cells11050765 -
Critical Reviews in Food Science and... 2023Anthocyanins are naturally occurring bioactive compounds found mainly in fruits, vegetables, and grains. They are usually extracted due to their biological properties... (Review)
Review
Anthocyanins are naturally occurring bioactive compounds found mainly in fruits, vegetables, and grains. They are usually extracted due to their biological properties and great potential for technological applications. These compounds have characteristic pH-dependent colorations that are natural dyes since they come in different colors. However, they are susceptible to processing conditions, remarkably light, temperature, and oxygen. The acylated anthocyanins showed better stability characteristics, and therefore, an acylation process of these compounds could improve their applications. The enzymatic acylation was effective and showed promising results. The current review provides an overview of the works that performed enzymatic acylation of anthocyanins and studies on the stability, antioxidant activity, and lipophilicity. In general, enzymatically acylated anthocyanins showed better stability to light and temperature than non-acylated compounds. In addition, they were liposoluble, a characteristic that allows their addition to products with lipid matrices. The results showed that these compounds formed by enzymatic acylation have perspectives of application mainly as natural colorants in food products. Therefore, the enzymatic acylation of anthocyanins appears viable to increase the industrial applicability of anthocyanins. There are still some gaps to be filled in process optimization, the reuse of enzymes, and toxicity analysis of the acylated compounds formed.
Topics: Anthocyanins; Antioxidants; Temperature; Acylation; Fruit
PubMed: 35191785
DOI: 10.1080/10408398.2022.2041541 -
Drug Resistance Updates : Reviews and... Dec 2020Histone modifications and more specifically ε-lysine acylations are key epigenetic regulators that control chromatin structure and gene transcription, thereby impacting... (Review)
Review
Histone modifications and more specifically ε-lysine acylations are key epigenetic regulators that control chromatin structure and gene transcription, thereby impacting on various important cellular processes and phenotypes. Furthermore, lysine acetylation of many non-histone proteins is involved in key cellular processes including transcription, DNA damage repair, metabolism, cellular proliferation, mitosis, signal transduction, protein folding, and autophagy. Acetylation affects protein functions through multiple mechanisms including regulation of protein stability, enzymatic activity, subcellular localization, crosstalk with other post-translational modifications as well as regulation of protein-protein and protein-DNA interactions. The paralogous lysine acetyltransferases KAT6A and KAT6B which belong to the MYST family of acetyltransferases, were first discovered approximately 25 years ago. KAT6 acetyltransferases acylate both histone H3 and non-histone proteins. In this respect, KAT6 acetyltransferases play key roles in regulation of transcription, various developmental processes, maintenance of hematopoietic and neural stem cells, regulation of hematopoietic cell differentiation, cell cycle progression as well as mitosis. In the current review, we discuss the physiological functions of the acetyltransferases KAT6A and KAT6B as well as their functions under pathological conditions of aberrant expression, leading to several developmental syndromes and cancer. Importantly, both upregulation and downregulation of KAT6 proteins was shown to play a role in cancer formation, progression, and therapy resistance, suggesting that they can act as oncogenes or tumor suppressors. We also describe reciprocal regulation of expression between KAT6 proteins and several microRNAs as well as their involvement in cancer formation, progression and resistance to therapy.
Topics: Acetylation; Animals; Disease Models, Animal; Embryonic Development; Histone Acetyltransferases; Histone Code; Histones; Humans; Lysine; Mice; Neurodevelopmental Disorders; Protein Processing, Post-Translational
PubMed: 33130515
DOI: 10.1016/j.drup.2020.100729 -
Journal of Molecular Biology Aug 2020S-acylation, whereby a fatty acid chain is covalently linked to a cysteine residue by a thioester linkage, is the most prevalent kind of lipid modification of proteins.... (Review)
Review
S-acylation, whereby a fatty acid chain is covalently linked to a cysteine residue by a thioester linkage, is the most prevalent kind of lipid modification of proteins. Thousands of proteins are targets of this post-translational modification, which is catalyzed by a family of eukaryotic integral membrane enzymes known as DHHC protein acyltransferases (DHHC-PATs). Our knowledge of the repertoire of S-acylated proteins has been rapidly expanding owing to development of the chemoproteomic techniques. There has also been an increasing number of reports in the literature documenting the importance of S-acylation in human physiology and disease. Recently, the first atomic structures of two different DHHC-PATs were determined using X-ray crystallography. This review will focus on the insights gained into the molecular mechanism of DHHC-PATs from these structures and highlight representative data from the biochemical literature that they help explain.
Topics: Acylation; Acyltransferases; Crystallography, X-Ray; Humans; Models, Molecular; Protein Domains; Protein Processing, Post-Translational
PubMed: 32522557
DOI: 10.1016/j.jmb.2020.05.023 -
Biochemical Society Transactions Jun 2024Protein mislocalization is a key initial step in neurodegeneration, regardless of etiology, and has been linked to changes in the dynamic addition of saturated fatty... (Review)
Review
Protein mislocalization is a key initial step in neurodegeneration, regardless of etiology, and has been linked to changes in the dynamic addition of saturated fatty acids to proteins, a process known as S-acylation. With the advent of new techniques to study S-acylation and the recent discovery of new enzymes that facilitate protein deacylation, novel small molecules are emerging as potential new therapeutic treatments. Huntington disease (HD) is a devastating, fatal neurodegenerative disease characterized by motor, cognitive, and psychiatric deficits caused by a CAG repeat expansion in the HTT gene. The protein that is mutated in HD, huntingtin, is less S-acylated which is associated with mutant HTT aggregation and cytotoxicity. Recent exciting findings indicate that restoring S-acylation in HD models using small molecule inhibitors of the deacylation enzymes is protective. Herein, we set out to describe the known roles of S-acylation in HD and how it can be targeted for therapeutic design.
Topics: Huntington Disease; Humans; Acylation; Huntingtin Protein; Animals; Fatty Acids
PubMed: 38695682
DOI: 10.1042/BST20231290 -
Open Biology Mar 2021Post-translational modifications (PTMs) such as phosphorylation and ubiquitination are well-studied events with a recognized importance in all aspects of cellular... (Review)
Review
Post-translational modifications (PTMs) such as phosphorylation and ubiquitination are well-studied events with a recognized importance in all aspects of cellular function. By contrast, protein S-acylation, although a widespread PTM with important functions in most physiological systems, has received far less attention. Perturbations in S-acylation are linked to various disorders, including intellectual disability, cancer and diabetes, suggesting that this less-studied modification is likely to be of considerable biological importance. As an exemplar, in this review, we focus on the newly emerging links between S-acylation and the hormone insulin. Specifically, we examine how S-acylation regulates key components of the insulin secretion and insulin response pathways. The proteins discussed highlight the diverse array of proteins that are modified by S-acylation, including channels, transporters, receptors and trafficking proteins and also illustrate the diverse effects that S-acylation has on these proteins, from membrane binding and micro-localization to regulation of protein sorting and protein interactions.
Topics: Acylation; Animals; Humans; Insulin; Insulin Secretion; Protein Processing, Post-Translational; Signal Transduction
PubMed: 33784857
DOI: 10.1098/rsob.210017 -
Methods (San Diego, Calif.) Sep 2019RNA is a regulator and catalyst of many cellular processes. Efforts to therapeutically harness RNA began with the discovery of myriad coding and non-coding RNAs and... (Review)
Review
RNA is a regulator and catalyst of many cellular processes. Efforts to therapeutically harness RNA began with the discovery of myriad coding and non-coding RNAs and their versatile modes of action. However, due to its dynamic structure and the polar and repetitive nature of its surface, RNA presents a challenging target for drug design. For an RNA to be druggable, it must contain a motif that assumes a nearly fixed and unique conformation that a small molecule can recognize and bind consistently and with high affinity. Hence, reliable methods for determining the secondary and tertiary structures of RNA, and even the features and occupancy of potential drug binding sites are of utmost importance for the effective design of RNA-based therapeutics. Selective 2'-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP) has emerged as such a method, by which RNA secondary structure can be probed at single-nucleotide resolution, under a variety of conditions, and in the presence of RNA-specific small-molecule ligands. In this review, we describe an in-depth protocol for using SHAPE-MaP to characterize RNA-small molecule interactions in cell culture (in cellulo). This method can be applied to transcripts of any size or abundance, and to determine the sites and affinities of small molecule binding, making it an essential and versatile tool for drug discovery.
Topics: Acylation; Humans; Ligands; Nucleic Acid Conformation; RNA; Sequence Analysis, RNA; Small Molecule Libraries
PubMed: 31009771
DOI: 10.1016/j.ymeth.2019.04.009