N-Methylation and N-Acetylation of Nonhistone Chromosomal Proteins
Lubomir S. Hnilica in Chromosomal Nonhistone Proteins, 2018
In recent years a large amount of information on acetylation of histones has become available (reviewed by Hnilica in The Structure and Biological Function of Histones). In addition, Ruiz-Carillo et al.70 and Isenberg71 have reviewed more recent work on this subject. Briefly, postsynthetic acetylation occurs on ϵ-amino groups of several internal lysine residues of histones 3 and 4. The acetyltransferases responsible for this process use acetyl-CoA as acetyl donor. The acetyl groups are continuously removed by a histone deacetylase, creating an active turnover of acetyl groups with half-lives ranging from a few minutes to several hours.72,73 Histones H1, H2A, and H4 are also acetylated N-terminally on the α-amino of serine, but this occurs during synthesis and these groups do not turn over. A number of substances, such as butyric acid and dimethylsulfoxide, have been found to induce hyperacetylation of histones. The basis for this phenomenon is the inhibitory effect of these substances on the histone deacetylase.71 A large amount of circumstantial evidence suggests a connection between histone acetylation and RNA synthesis. In addition, hyperacetylation renders chromatin more susceptible to attack by DNAse I, an enzyme which preferentially digests active genes.71
Genetics and Biosynthesis of Lipopolysaccharide O-Antigens
Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison in Endotoxin in Health and Disease, 2020
Polysaccharide modification by glycosyl and non-carbohydrate substituents may be stoichiometric or nonstoichiometric, and the difference most likely lies in the stage of biosynthesis at which the substitution reaction occurs. In the case of Salmonella serogroups E and B, in vitro and in vivo studies have both shown that incorporation of the stoichiometric side-branch sugars occurs prior to completion of the O unit and the subsequent polymerization reactions. Studies with sero-group B strains unable to produce the side chain precursor, CDP-abequose, fail to produce O-PS (56). The donor for nonstoichiometric glucosyl substituents in S. enterica O-PSs is an unusual lipid intermediate, a-glucosylmonophosphorylundecaprenol (57–59). In sero-groups B and D, glucosylation occurs postpolymerization and is assumed to occur at the level of the O-hapten (Und-PP-linked O-PS) (58–61). In contrast, in serogroups Cl and C2, glucosylation occurs before polymerization, at the level of individual Und-PP-linked O units (62). O-Acetylation has been studied in S. enterica serogroup El both in vivo (63) and in vitro (64). The donor for the acetyl group is acetyl-CoA, and the substrate for the acetyltransferase reaction is the single Und-PP-linked O unit.
The Opioid Epidemic
Sahar Swidan, Matthew Bennett in Advanced Therapeutics in Pain Medicine, 2020
Morphine also impacts epigenetic mechanisms that result in hyperalgesia and tolerance by changes in long-term gene expression in the pain system. Histone acetylation and deacetylation help to control gene expression. Histone acetyltransferase (HAT) enzymes transfer an acetyl group onto histones. The result is a more relaxed chromatin structure (euchromatin) and greater gene transcription. This relaxed structure can be “undone” by histone deacetylase (HDAC) transforming to a more condensed form (heterochromatin). Increasing morphine dose enhances the expression of acetylated histone H3 lysine9 (aceH3K9) in the dorsal spinal cord, which regulates the expression of dynorphin and brain-derived neurotrophic factor (BDNF).21 HAT inhibitors prior to morphine exposure (such as curcumin) have reduced the development of opioid-induced hyperalgesia.1,22 Conversely, HDAC inhibitor injections after morphine exposure prolong the morphine hyperalgesia and tolerance.22 Preventing the acetylation of histones or blocking BDNF or dynorphin may reduce hyperalgesia.
Gene expression profiling of rat livers after continuous whole-body exposure to low-dose rate of gamma rays
Published in International Journal of Radiation Biology, 2018
Acetyl-CoA is at the center of lipid metabolism. Cytosolic acetyl-CoA synthesis, which is essential for de novo lipogenesis, was reduced in response to the low-dose-rate radiation. The cytosolic pool of acetyl-CoA is mainly supplied by two different ATP-dependent reactions: cleavage of citrate, which is generated from TCA cycle, into oxaloacetate and acetyl-CoA by ATP citrate lyase (ACLY) or the ligation of acetate and CoA by acetyl-CoA synthetase (ACSS) (Schug et al. 2015). Both ACLY and ACSS2, the cytosolic ACSS, were transcriptionally down-regulated in this study. Another pathway in producing cytosolic acetyl-CoA was through converting acetoacetate to acetoacetyl-CoA by acetoacetyl-CoA synthetase (AACS) and subsequently to acetyl-CoA by acetyl-CoA acetyltransferase 2 (ACAT2). This acetyl-CoA synthesis was also decreased as both Aacs and Acat2 genes were down-regulated.
Current trends in protein acetylation analysis
Published in Expert Review of Proteomics, 2019
Issa Diallo, Michel Seve, Valérie Cunin, Frédéric Minassian, Jean-François Poisson, Sylvie Michelland, Sandrine Bourgoin-Voillard
Because post-translational modifications (PTMs) are involved in many biological processes and can regulate the protein function by changing stability, localization and activity of proteins, their analysis is critical to understand regulation of biological processes [1]. Among those PTMs, acetylation, discovered in 1963 by Phillips et al. [2], has emerged as one of the major protein PTMs in the cell after phosphorylation [3]. Acetylation is catalyzed by a wide range of acetyltransferases (such as Enzyme Class EC 2.3.1) that transfer acetyl groups (–CO–CH3) from an acetylated molecule like acetyl-coenzyme A onto specific amino acids, which results in addition of an acetyl group on modified species to account for an additional 42 Da [4]. Three major types of acetylation have been described based on the acetylation site in the protein (Figure 1), including: (a) N-terminal acetylation commonly named N-ter acetylation or Nα-acetylation; (b) lysine acetylation commonly named K-acetylation (KAc) or Nε-acetylation; (c) O-acetylation.
Protein lysine acetylation and its role in different human pathologies: a proteomic approach
Published in Expert Review of Proteomics, 2021
Orlando Morales-Tarré, Ramiro Alonso-Bastida, Bolivar Arcos-Encarnación, Leonor Pérez-Martínez, Sergio Encarnación-Guevara
The lysine acetyltransferases and histone acetylation were discovered in 1964 by Allfrey and colleagues [23]. They were originally described for their ability to acetylate histone-proteins, which is why they were initially being called HATs. However, they have now been renamed lysine acetyltransferases (KATs). This class of enzymes acetylate conserved lysine residues in target proteins by transferring an acetyl group from AcCoA to the epsilon amino group of the side chains of lysine residues [23]. Despite recent advances in research related to acetylation, the precise quantity of acetyltransferases present in the human cell remains unknown. Three groups of proteins constitute the KAT family: the first group is the GNAT family (GCN5-related N-acetyltransferase). The MYST family (monocytic leukemia zinc finger protein (MOZ), Tip60, Sas2, Sas3/Ybf2) makes up the second group, and p300/CREB-binding protein (CBP) family constitute the last group [24]. KATs have domains additional to the catalytic domain, which interact with other proteins and substrates, including bromodomains and other modification recognition domains [25]. Histones are not the unique targets recognized for KAT enzymes; several transcription factors, coregulators of transcription, in addition to enzymes implied in central metabolic pathways, can be modified by them [26]. Table 1 describes the different KAT families and some of their properties compiled in uniprot database.
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