Lysine, carboxyl activation

Hayama et al.132 discussed the catalytic effects of silver ion-polyacrylic add systems toward the hydrolyses of 2,4-dinitrophenylvinylacetate 84 (DNPVA) by using the weak nudeophilicity of carboxylic groups and the change-transfer interactions between olefinie esters and silver ions133Metal complexes of basic polyelectrolytes are also stimulating as esterase models. Hatano etal. 34, 13S) reported that some copper(II)-poly-L-lysine complexes were active for the hydrolyses of amino acid esters, such as D- and L-phenylalanine methyl ester 85 (PAM). They... 

Class D enzymes (Mr of about 27,000) exhibit a high activity versus isoxazolyl penicillins, such as oxacillin and are referred to as the OXA-family. Surprisingly, the amino group of the SXXK lysine residues is carboxylated in the most active forms of the enzymes. Penicillins are generally better substrates than cephalosporins but mutations have been found which confer extended activity spectra to these enzymes. 

Small tfbiquitin-like modifier represents a family of evolutionary conserved proteins that are distantly related in amino-acid sequence to ubiquitin, but share the same structural folding with ubiquitin proteins. SUMO proteins are covalently conjugated to protein substrates by an isopeptide bond through their carboxyl termini. SUMO addition to lysine residues of target proteins, termed SUMOylation, mediates post-transla-tional modification and requires a set of enzymes that are distinct from those that act on ubiquitin. SUMOylation regulates the activity of a variety of tar get proteins including transcription factors. 

The inhibition of C a2+-ATPase at the active site by ATP-Im or ADP-Im with the participation of Ca2+ is illustrated by the following model. In the reaction of ATP-imidazolide with the carboxylate of Asp 351, a mixed anhydride is formed with the aspartate residue, followed by presumably nucleophilic attack of a lysine side chain, thereby displacing the nucleotide and leading to an intramolecular crosslink.[1]... 

Some enzymes are nonfunctional until posttranslationally modified. Examples of these enzymes include the acyl- and carboxyltransferases. While lipoate and phosphopantetheine are necessary for acyl transfer chemistry, tethered biotin is used in carboxyl transfer chemistry. Biotin and lipoate tethering occur under a similar mechanism the natural small molecule is activated with ATP to form biotinyl-AMP or lipoyl-AMP (Scheme 20). A lysine from the target protein then attacks the activated acid and transfers the group to the protein. The phosphopantetheine moiety is transferred using its own enzyme, the phosphopantetheinyltrans-ferase (PPTase). The PPTase uses a nucleophilic hydroxy-containing amino acid, serine, to attach the phosphopantetheinyl (Ppant) arm found in coenzyme A to convert the apo (inactive) carrier protein to its holo (active) form. The reaction is Mg -dependent. 

Protein biotinylation is catalyzed by biotin protein ligase (BPL). In the active site of the enzyme, biotin is activated at the expense of ATP to form AMP-biotin the activated biotin can then react with a nucleophile on the targeted protein. BPL transfers the biotin to a special lysine on biotin carboxyl carrier protein (BCCP), a subunit of AcCoA carboxylase (Scheme 21). Biotinylation of BCCP is very important in fatty acid biosynthesis, starting the growth of the fatty acid with AcCoA carboxylase to generate malonyl-CoA. Recently the crystal structures of mutated BPL and BCCP have been solved together with biotin and ATP to get a better idea of how the transfer fiinctions. ... 

---