Lysin aromatic residues

More specific evidence came from affinity labeling with molecules which could react with specific amino acid group sat or adjacent to the substrate site. These labels were substrate analogues and competitive inhibitors. Substituted aryl alkyl ketones were used. TV-p-toluene-sulphonyl-L-phenylalanine chloromethyl ketone (TPCK) blocked the activity of chymotrypsin. Subsequent sequence analysis identified histidine 57 as its site of binding (see Hess, 1971, p 213, The Enzymes, 3rd ed.). Trypsin, with its preference for basic rather than aromatic residues adjacent to the peptide bond, was not blocked by TPCK but was susceptible to iV-p-toluenesulphonyl-L-lysine chloromethyl ketone (TLCK) (Keil, ibid, p249). 

In the digestive system trypsin, chymotrypsin, and elastase work as a team. They are all endopeptidases, which means that they cleave protein chains at internal peptide bonds, but each preferentially hydrolyses bonds adjacent to a particular type of amino acid residue (fig. 8.4). Trypsin cuts just next to basic residues (lysine or arginine) chymotrypsin cuts next to aromatic residues (phenylalanine, tyrosine, or tryptophan) elastase is less discriminating but prefers small, hydrophobic residues such as alanine. 

Trypsin, chymotrypsin, and elastase—three members of the serine protease family—catalyze the hydrolysis of proteins at internal peptide bonds adjacent to different types of amino acids. Trypsin prefers lysine or arginine residues chymotrypsin, aromatic side chains and elastase, small, nonpolar residues. Carboxypeptidases A and B, which are not serine proteases, cut the peptide bond at the carboxyl-terminal end of the chain. Carboxypeptidase A preferentially removes aromatic residues carboxypeptidase B, basic residues. (Illustration copyright by Irving Geis. Reprinted by permission.)... 

The vertebrate pancreatic carboxypeptidases are one such family of digestive enzymes. Within the family, two broad substrate preferences are known. Enzymes with carboxypeptidase A (CPA) activity cleave hydro-phobic and aromatic residues from the carboxyl terminus of peptides and proteins, whereas those with carboxypeptidase B (CPB) activity prefer substrates with arginine and lysine residues at the C terminus.3 Several duplicates within the family have CPA-like activity but display a range of substrate preferences.5,6... 

Some residues, such as Gly and aromatic residues significantly destabilize the triple helix. Galactosylations of threonine (9) and that of the lysine (10) increases the stability of the triple helix.Regarding the stabilizing effect of 4(R)-hydroxyproline on the triple helix, studies with model peptides showed that the order of the stability of the triple helix is -Gly-Pro (R)Flp- >... 

The NMR data assume explicitly that the aromatic residues are the only source of their observed shifts, and their model involves placing four aromatic residues in the vicinity of the DNP hapten (Fig. 15B). It will be important to verify this assumption, since there are many other causes for NMR shifts. It should be noted that the conformation of the e DNP lysine in the two models is not the same (Figs. 15A and 15B). 

These studies support the idea that the bilayer is actually somewhat permeable to macromolecules under certain conditions. The exact mechanism of this permeability is not known, but the arginine specificity of nonclassical vectors (see Section 13.4.1.1) suggests a reasonable pathway. Although these side chains are not expected to interact with the apolar interior of the bilayer, they may interact with the numerous transmembrane proteins that span biological membranes. The helices of membrane-spanning proteins are often found to be studded with aromatic residues,158 160 providing an ideal environment for the formation of cation-7t interactions between arginine (and potentially lysine) residues of a vector and the... 

In the past ten years, there has been developed a series of enzyme inhibitors that combine the features of an alkylating agent with specificity for the active site of an enzyme, thus permitting alkylation and identification of a group at or near the active center of an enzyme, or a particular enzyme to be specifically inactivated. Thus a l-chloro-4-phenyl-3-p-toluenesulfonamido-2-butanone ( W-p-tolylsulfonylphenylalanine chloro-methyl ketone ) inactivates chymotrypsin (which cleaves a peptide bond adjacent to an aromatic residue), and 7-amino-l-chloro-3-p-toluene-sulfonamido-2-heptanone ( a-iV-p-tolylsulfonyllysine chloromethyl ketone ) inhibits trypsin (which cleaves a peptide bond adjacent to lysine. In both cases, a histidine residue at the active site is alkylated, and neither inhibitor will inhibit the other enzyme at low concentrations. 

Bearing in mind that the thickness of the lipid bilayer of a bacterial membrane is approximately 30 A and that the antimicrobial activity and sdectivity of AMPs seemed to be driven predominantly by physiochemical parameters, in 2003 Patch and Barron designed peptoids to mimic the fadally amphipathic stmcture of the cationic, 23-mer AMP magainin-2. Magainin-2 has three distinct faces that are, respertivdy, rich in hydrophobic aliphatic residues, aromatic residues, and basic residues (lysines) (Figure 14). The threefold periodicity of... 

The structure of rat P450c24 at 2.5 A resolution shows an open cleft flanked by conserved hydrophobic residues on helices A and G, with a membrane-directed substrate-access chatmel, stabilized by corrserved aromatic residues on helices B, F and G, leading to the heme. Docking of 1,25(0H)2D shows that the hydrophobic substrate fits well in this channel. The proximal surface of P450c24 contains basic residues from the K, K", and L helices and an adjacent lysine-rich loop that define the adrenodoxin binding site... 

Many proteins contain hundreds of amino acids. To determine their sequences other reactions are required to provide sequences short enough to be determined by Edman degradation. Enzymatic cleavage by two enzymes, trypsin and chymotrypsin, is used to produce smaller peptides. Trypsin cleaves polypeptide chains on the C-terminal side of basic residues such as arginine and lysine. Chymotrypsin cleaves the polypeptide on the C-terminal side of aromatic residues. 

Ring current effects have been observed in the cyclic peptide hormone lysine vasopressin in aqueous solution. Proximity of the two aromatic residues produces perturbations of 0.12 and 0.19 ppm on the chemical shifts of the ortho and meta protons of the tyrosyl residue when compared with oxytocin analogues not containing the aromatic phenylalanyl residue... 

---