Arginine residues modification

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... 

The ability to direct conjugation or modification specifically through arginine residues using this chemistry has been exploited in the availability of the only photoreactive glyoxal derivative, APG. 

Konishi, K., and Fujioka, M. (1987) Chemical modification of a functional arginine residue of rat liver glycine methyltransferase. Biochemistry 26, 8496-8502. 

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. 

Cholera toxin catalyzes the ADP-ribosylation of a specific arginine residue in G and Gat. This covalent modification inhibits the intrinsic GTPase activity of these a subunits and thereby freezes them in their activated, or free, state (Fig. 19-1C). By this mechanism, cholera toxin stimulates adenylyl cyclase activity and photoreceptor transduction mechanisms. The ability of cholera toxin to ADP-ribosylate G may require the presence of a distinct protein, ADP-ribosylation factor (ARF). ARF, which is itself a small G protein (Table 19-2), also is ADP-ribosylated by cholera toxin. ARF is implicated in controlling membrane vesicle trafficking (see Ch. 9). 

A high proportion of the positiveiy charged basic amino acids lysine and arginine within these flexible tails are frequent targets for extensive posttranslational modifications (Berger, 2002). Such modifications include the acetylation of lysine residues, the methylation of lysine and arginine residues, the ubiquitination of lysine residues, the phosphorylation of serine and threonine residues, the sumoylation of lysine residues, and the poly ADP-ribosylation of glutamic acid residues. 

Histone methylation is another posttranslational modification which involves a transfer of a methyl group from the methyl donor S-adenosyl methionine (SAM) to lysine or arginine residues (Fig. 1). In sharp contrast with histone acetylation, this modification occurs particularly in histones H3 and H4 with a remarkable specificity (Kouzarides, 2002 Shilatifard, 2006) (Fig. 1, Table 2). Another feature of histone methylation is that a large fraction of histones in mature chromatin is... 

Arginine residues are very resistant to most of the usual reagents used for chemical modification. King (166) has reported the conversion of these residues to S-N- (2-pyrimidinyl) ornithine by treatment with malonaldehyde in 10 N HC1. Essentially complete modification of the 4 arginine residues in RNase was obtained. Peptide bond cleavage and disulfide interchange also occurred, however, and no conclusions are warranted on the relation of the properties of the product to the actual arginine modification. 

In addition to acetylation/deacetylation, there are numerous other histone modification scenarios. For example, histones can be methylated or unmethylated at lysine, serine, and arginine residues located in the... 

G-protein a-subunits also possess specific residues that can be covalently modified by bacterial toxins. Cholera toxin catalyzes the transfer of ADP-ribose moiety of NAD to a specific arginine residue in certain a-subunits, whereas pertussis toxin ADP-ribosylates those a-subunits that contain a specific cysteine residue near the carboxy-terminus. Modification of the a-subunit by cholera toxin persistently activates these protein by inhibiting their GTPase activity, whereas pertussis toxin inactives Gia protein and thereby results in the uncoupling of receptor from the effector. G-protein a-subunits are regulated by covalent modifications by fatty acids myristate and palmate. These lipid modifications serve to anchor the subunits to the membrane and increase the interaction with other protein and also increase the affinity of the a-subunit for 3y. In this regard, the myristoylation of Gia is required for adenylyl cyclase inhibition in cell-free assay (Taussig et al. 1993). 

Imidazole rings appear in a number of physiological modifications of arginine residues (see Chapter 8). Some imidazoles elicit undesirable physiological responses (see Chapter 6). 

Both ornithine, which is a homologue of lysine, and citrulline are L-amino acids, but neither has a genetic codon, and both are found only as posttranslational modifications of arginine residues in some proteins such as keratin. Citrulline leaves the mitochondria by the same transport system that facilitates ornithine s entry from the cytoplasm. 

Another hydroxylated product of OH modification of proline is 5-hydroxy-2-aminovaleric acid, arising from oxidation of proline and arginine residues (A20) (Fig. 4). 

A fairly recent and fascinating family of reactions is the incorporation of ADP-ribosyl into proteins as shown in Figure 3. In the ADP-ribosylation of IJ. coli DNA dependent RNA polymerase upon infection with bacteriophage T4 (32, 33), the reaction requires NAD+ and proceeds with the concomitant release of nicotinamide and a proton. The effect of the modification reaction is to turn off host transcription. Two arginine residues were... 

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