Reversible modification of lysine

Shetty, J.K., and Kinsella, J.E. (1980) Ready separation of proteins from nucleoprotein complexes by reversible modification of lysine residues. Biochem. J. 191, 269-272. 

Pathy, L., and Smith, E.L. (1975) Reversible modification of arginine residues Application to sequence studies by restriction of tryptic hydrolysis to lysine residues./. Biol. Chem. 250, 557. 

Reversible Modification of Amino Groups of Lysine in Yeast Proteins Using Citraconic and Maleic Anhydrides... 

Another approach, artificial hydrophobization of polypeptides with a small number of fatty acid residues (e.g. stearate or palmitate) has been showm to enhance cellular uptake (Kabanov et al., 1989a). Specifically, this technique involves point modification of lysine or N-terminal amino groups with one or two fatty acid residues per protein molecule. As a result of such modification, the protein molecule remains water-soluble but also acquires hydrophobic anchors that can target even very hydrophilic proteins to cell surfaces (Slepnev et al., 1995). To obtain low and controlled degrees of modification, a system of reverse micelles of a surfactant, sodium bis-(2-ethyIhexyl)sulfosucciate (Aerosol OT) in octane was used as a reaction medium (Kabanov et al., 1987) (Figure 47.4). Over a... 

Yost and Harrison (118) have reported that m-MDH is irreversibly inactivated by pyridoxal 5 -phosphate (PLP). In view of the usual reversibility of this reagent when reacted with the -amino group of lysine, and the unusual spectral properties of the derivative formed, it was concluded that the reaction of m-MDH with PLP proceeds via modification of lysine followed by the formation of a secondary stable complex. Such a complex might be a thiazolidine-like compound formed by the reaction of the Schiff base with a neighboring cysteinyl residue. The role of the lysine residue in the active site of m-MDH remains to be clarified. 

ADP—ribosyltransferases modify the activity of target enzymes by catalysing the transfer of ADP—ribose onto arginine, lysine or asparagine residues. ADP—ribosylation is a reversible modification of proteins, and there are specific hydrolases which cleave the N-glycoside linkage. 

Histone acetylation is a reversible and covalent modification of histone proteins introduced at the e-amino groups of lysine residues. Histones and DNA form a complex - chromatin - which condenses DNA and controls gene activity. Current models interpret histone acetylation as a means to regulate chromatin activity. 

Histone methylation is a common posttranslational modification fond in histones. Histone methylations have been identified on lysine and arginine residues. In case of lysines S-adenosyl-methionine (SAM) dependent methyl transferases catalyze the transfer of one, two or three methyl groups. Lysine methylation is reversible and lysine specific demethylases have been... 

Posttranslational modifications can be broken down into two main classes those that are reversible and those that are irreversible. Included in the large group of reversible posttranslational modifications are phosphorylation, acetylation, and disulfide formation. Irreversible posttranslational modifications include peptide bond cleavage as in intein splicing also irreversible is the introduction of a phosphopantetheinyl group during fatty acid, polyketide, and nonribosomal peptide biosyntheses. The current debate is whether to classify lysine N-methylation as reversible or irreversible. Recently, there have been reports of lysine demethylases. ... 

Acetylation is a reversible modification on proteins that can also contribute to protein localization and function. Acetylation of lysine residues in histone proteins can control the secondary structure of chromatin as well as gene expression levels from certain loci, and chromatin remodeling and its consequences in a variety of molecular and cell biological questions are intensely researched. Many other proteins undergo reversible acetylation, and the functional consequences of these modifications are poorly understood in many cases. 

Another speculation has been put forth. Because the turnover of methyl groups such as the modification on lysine residues is low, ubiquitination of histone N-termini might serve as a signal for proteolysis of methylated histones such that dynamic regulation of the chromatin is possible. Since no histone demethylases have been identified, ubiquitin-mediated proteolysis might be a way to reverse the effects of histone methylation. ... 

In the recent literature, many examples of A/BPs containing benzophenones can be found. A first example concerns the study of HDACs. These enzymes catalyze the hydrolysis of acetylated lysine amine side chains in histones and are thus involved in the regulation of gene expression. There are approximately 20 human HDACs, which are divided into three classes (I, II, and III). Class I and II HDACs are zinc-dependent metallohydrolases that do not form a covalent bond with their substrates during their catalytic process, which is similar to MMPs. It has been found that hydroxamate 65 (SAHA, see Fig. 5) is a potent reversible inhibitor of class I and II HDACs. In 2007, Cravatt and coworkers reported the transformation of SAHA into an A/BP by installment of a benzophenone and an alkyne moiety, which resulted in SAHA-BPyne (66) [73]. They showed that the probe can be used for the covalent modification and enrichment of several class I and class II HDACs from complex proteomes in an activity-dependent manner. In addition, they identified several HDAC-associated proteins, possibly arising from the tight interaction with HDACs. Also, the probe was used to measure differences in HDAC content in human disease models. Later they reported the construction of a library of related probes and studied the differences in HDAC labeling [74], Their most... 

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