Introduction to Cell Biology
Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George in The Scientific Basis of Urology, 2010
SUMO (small ubiquitin-related modifier) is a small molecular weight protein that is structurally related to ubiquitin, and indeed many similarities exist between the two in terms of ligation and lysine attachment. The role of SUMOylation appears to be substrate specific; however, it has been implicated as a negative regulator of transcription, potentially by promoting the interaction of transcription factors with corepressors. Cross talk with another mechanism of posttranslation modification, acetylation, may compete with SUMO for binding, and many have antagonistic effects. Acetylation occurs when an acetyl group (CH3CO) is covalently attached to lysine and this process is catalyzed by a group of enzymes known as acetyl transferases. Acetylation protects proteins from rapid digestion by intracellular proteases, although other functions for this modification are being revealed.
Nucleic Acids as Therapeutic Targets and Agents
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
The other important epigenetic mechanism is histone acetylation/deacetylation. The attraction of methyl-binding domain (MBD) proteins associated with histone deacetylases (HDACs) represents a more generalized effect, as the chromatin structure can be completely changed by these enzymes, profoundly affecting the expression of more than one gene. This process, known as chromatin remodeling, involves acetylation of the chromatin causing it to “open” and become more accessible to the necessary transcription factors, thus promoting gene expression. Conversely, gene silencing results from deacetylation of the histones, which causes the condensation of chromatin due to the positively charged lysine amino groups released interacting with the negatively charged DNA (Figure 5.108).
Candidate Genes, Gene × Environment Interactions, and Epigenetics
Gail S. Anderson in Biological Influences on Criminal Behavior, 2019
Histone modification has an indirect impact on the genomic DNA. Histones are proteins involved in the packaging of DNA, which is an extremely long molecule. They are the basic core around which DNA is wrapped.48 Histones spool and package the DNA and organize it into chromosomes. Histone modification, or acetylation, involves attaching an acetyl group (CH3CO) to certain histone sites, which results in a loosening of the chromatin that packages DNA within a cell, impacting transcription, the first part of gene expression. This tells other proteins whether this part of the DNA molecule should be turned on or off and often increases gene expression.
N-acetyltransferase: the practical consequences of polymorphic activity in man
Published in Xenobiotica, 2020
Stephen C. Mitchell
Acetylation (ethanoylation) is the introduction of an acetyl group into a compound via the replacement of active hydrogen to form an acetoxy derivative. With regards to foreign compound metabolism, the acetylation of both nitrogen centres within the amino groupings of arylamines and arylhydrazines and oxygen centres of arylhydroxylamines, have been reported. In addition, a transacetylation reaction known as “acetylhydroxyamic acid acetyl transfer” (AHAT) may occur where the already present acetyl group undergoes intramolecular movement from the nitrogen of an arylhydroxamic acid, to the oxygen in the same molecule thereby producing an acetoxy arylamine (Land & King, 1994). The existence of S-acetyl compounds such as acetyl-CoA are known in intermediary metabolism but have not been reported as metabolites of drug molecules.
Highly effective biosynthesis of N-acetylated human thymosin β4 (Tβ4) in Escherichia coli
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Rui Yu, Sai Cao, Yanhong Liu, Xinxi Si, Ting Fang, Xu Sun, Hongmei Dai, Junjie Xu, Hongqing Fang, Wei Chen
Acetylation is a ubiquitous protein modification, which has an important influence on the protein activity and stability. In some cases, the lack of acetylation can lead to the decrease of protein thermal stability, complex assembly efficiency and the change of dynamic parameters [34]. For polypeptide drugs, the acetylation modification can improve the half-life of peptides in vivo [35]. Although in vitro studies indicated that non-acetylated Tβ4 also had partial biological activity, the acetylation modification could greatly increase the stability of Tβ4 in vivo. The rhTβ4 produced by Prospec (catalogue number: HOR-003), a recombinant expression product in E. coli without N-acetylation, could be stored at 4 °C only between 2 ∼ 7 days upon reconstitution, while the recombinant N-acetylated rhTβ4 produced in this study could be stable at 2–8 °C for 24 months in PBS buffer without protein degradation and concentration change. Accordingly, N-acetylation has an important influence on the stability of rhTβ4, which is the key point for rhTβ4 being developed into a drug.
Human carbonic anhydrases and post-translational modifications: a hidden world possibly affecting protein properties and functions
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Anna Di Fiore, Claudiu T. Supuran, Andrea Scaloni, Giuseppina De Simone
Protein acetylation is one of the most represented PTMs in the cell. In reactions catalysed by various N-terminal and lysine acetyltransferases, the acetyl group of the metabolite acetyl-coenzyme A is co- or post-translationally adducted to either the α-amino group of proteins or to the ε-amino group of corresponding K residues112. In the latter case, the reaction can be reverted by deacetylases through tightly-regulated and metabolism-dependent mechanisms. The interplay between acetylation and deacetylation is crucial for many important cellular processes. Since it converts a positively-charged group into a neutral moiety, acetylation can alter the structural conformation of a protein as well as its capability to interact with other molecules, with a possible impact on corresponding function. Accordingly, acetylation can regulate a number of metabolic and physiological processes, with a profound impact on cell and organism life.
Related Knowledge Centers
- Acetate
- Acetic Acid
- Chemical Compound
- Chemistry
- Ester
- Gene Expression
- Histone Acetylation & Deacetylation
- Lysine
- Cancer
- Post-Translational Modification
- Histone Acetylation & Deacetylation