Protein deacetylation

In addition to butyrate, trichostatin A, and trapoxin B, other small-molecule inhibitors of protein deacetylation have been identified from both natural and... 

Fig. 6-20 Forward chemical-genetic screen for inhibitors of protein deacetylation (data from Ref. 80). (a) Overview of cell-based screens of the 1,3-dioxane-based, diversity-oriented synthesis-derived library using antibodies to measure tubulin and histone acetylation, (b) Relative position of selected active compounds in a three-dimensional principal component model computed from five cell-based assay descriptors. AcTubulin-selective (red),...

Finally, inhibition of protein deacetylation with histone deacetylase (HDAC) inhibitors has shown promise in preclinical models of cardiovascular and renal disease, including myocyte hypertrophy, fibrosis, inflammation and epithelial-to-mesenchymal transition." ... 

Bao, J., Sack, M. (2010) Protein deacetylation by sirtuins delineating a post-translational regulatory program responsive to nutrient and redox stressors. Cellular and... 

Figure 7.5 Adenosine diphosphate (ADP)-ribosylation biochemical reactions. Mono-ADP-ribosyltransferases (ARTs) and poly-ADP-ribose pol5mierases Poly (PARPs) catalyse the ADP-ribose moiety of NAD transfer to amino acid residues. ADP-ribosyl cyclases generate cyclic ADP-ribose and 2-phospho-cyclic ADP-ribose from NAD and NADP, respectively. Both molecules trigger cyclic ADP-ribose cytosolic Ca " elevation, presumably by activating the ryanodine receptor in the endoplasmic/sarcoplasmic reticulum (RER). SIRTl catalyses a reaction that couples protein deacetylation to NAD hydrolysis.

The core unit of the chromatin, the nucleosome, consists of histones arranged as an octamer consisting of a (H3/ H4)2-tetramer complexed with two histone H2A/H2B dimers. Accessibility to DNA-binding proteins (for replication, repair, or transcription) is achieved by posttranslational modifications of the amino-termini of the histones, the histone tails phosphorylation, acetylation, methylation, ubiquitination, and sumoyla-tion. Especially acetylation of histone tails has been linked to transcriptional activation, leading to weakened interaction of the core complexes with DNA and subsequently to decondensation of chromatin. In contrast, deacetylation leads to transcriptional repression. As mentioned above, transcriptional coactivators either possess HAT activity or recruit HATs. HDACs in turn act as corepressors. 

Isolated chitins are highly ordered copolymers of 2-acetamido-2-deoxy-/3-D-glucose and 2-amino-2-deoxy-j6-D-glucose. The occurrence of the latter is explained by the fact that in vivo chitin is covalently finked to proteins via the nitrogen atom of approximately one repeating unit out of ten, therefore upon isolation a degree of deacetylation close to 0.10 is found. Chito-biose, 0-(2-amino-2-deoxy-j6-D-glucopyranosyl)-(l 4)-2-amino-2-deoxy-... 

The deacetylated protein should be used immediately to prevent loss of sulfhydryl content through disulfide formation. The degree of—SH modification may be determined by performing an Ellman s assay (Section 4.1, this chapter). 

Figure 1. Mechanistic effect of acetylation/deacetylation of histones and nonhistones on chromatin stracture.(a) Acetylation of non-histone proteins results in transcriptional activation (b) Acetylation of ORCl by HBOl is important for replication, (c) Acetylation of newly synthesized...

Reversible acetylation of histone and nonhistone proteins play key role in maintaining cellular homeostasis. In this following section we shall discuss about the physiological significances of acetylation and deacetylation of different classes of nonhistone proteins. 

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