Arginine target residues

In proteins, targets for methylation include lysine, arginine, and residues containing free carboxyl groups. Histones (chromatin proteins), for example, become methylated at specific arginine and lysine residues at particular times in the cell cycle (see here). s-N-Trimethyllysine, which is derived specifically from the hydrolysis of methylated proteins, is a precursor of carnitine, which transports fatty acyl moieties across membranes (see here). 

Cleavage occur s at the scissile bond. Residues in the substrate towards the N-terminus are numbered PI, P2, P3, etc, whereas residues towards the C-terminus are numbered PI, P2, P3 etc. Cleavage occurs between PI and P1. For a peptidase with limited specificity, only the residue in PI or PI is important for specificity. A peptidase with an extended substrate binding site will have a preference for residues in other positions. For example cathepsin L prefers substrates with phenylalanine in P2 and arginine in PI. However, this is a preference only, and cathepsin L cleaves substrates after other amino acids. Caspase-3 has a preference for Asp in both P4 and PI, but it is unusual for substrate specificity to extend much further from the scissile bond. The peptidase with the most extended substrate specificity may be mitochondrial intermediate peptidase that removes an octopeptide targeting signal from the N-terminus of cytoplasmically synthesized proteins that are destined for import into the mitochondrial lumen. 

It is noteworthy that there is another limiting factor in the choice of amino acid types at the junction sites which affect the enzymatic process of the intein. For example, in the case of SceVMA (also called PI-Seel) from the IMPACT system, proline, cysteine, asparagine, aspartic acid, and arginine cannot be at the C-terminus of the N-terminal target protein just before the intein sequence. The presence of these residues at this position would either slow down the N-S acyl shift dramatically or lead to immediate hydrolysis of the product from the N-S acyl shift [66]. The compatibility of amino acid types at the proximal sites depends on the specific inteins and needs to be carefully considered during the design of the required expression vectors. The specific amino acid requirements at a particular splicing site depends on the specific intein used and is thus a crucial point in this approach. 

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. 

All of the available evidence indicates that it is the sequence of a protein that determines its destination. Proteins targeted to pass through the inner mitochondrial or chloroplast membrane have 20- to 70-residue presequences that are rich in arginine and lysine and which are removed when the protein reaches its... 

All amino-acid residues of proteins are potential targets for attack by reactive oxygen species (ROS) produced in the radiolysis of water however, in only a few cases have the oxidation products been fully characterized. Moreover, under most physiological conditions, cysteine, methionine, arginine, lysine, proline, histidine, and the aromatic amino acids are primary targets for ROS-mediated oxidation. 

Trypsin cleaves a peptide bond on the C-terminal side of a basic residue such as arginine (Arg) or lysine (Lys) whereas chymotrypsin cleaves on the C-terminal side of the hydrophobic residues phenylalanine (Phe), tryptophan (Trp) or tyrosine (Tyr). Elastase cleaves on the C-terminal side of small amino acids such as alanine (Ala) and glycine (Gly). A large number of serine PI proteins have been isolated from plants (Table 13.4) and the substrate specificity of the target proteases corresponds with the inhibitory amino acid sequences (P2-P1-PT-P2 ) of the PI proteins. Thus, the double-headed trypsin- and chymotrypsin-inhibitory Bowman-Birk PI protein 1 (BBI-1) from soybean (Glycine BBI-1, Table 13.5G) has a Pl-PT sequence of Lys—Ser at the trypsin inhibitory domain I site and a PI PI sequence of Leu-Ser at the chymotrypsin inhibitory domain II site. 

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