Aromatic groups, hydrophobic amino acids

Microbial proteinases can be classified by mechanism of action. Hartley (1960) divided them into four groups serine proteinases, thio proteinases, metalloproteinases, and acid proteinases. Morihara (1974) classified enzymes within these groups according to substrate specificity. Enzymes which split peptide substrates at the carboxyl side of specific amino acids are called carboxyendopeptidases, and those which split peptide substrates at the amino side of specific amino acids are called aminoendopeptidases. Acid proteinases, such as rennin and pepsin, split either side of specific aromatic or hydrophobic amino acid residues. The action of proteolytic enzymes on milk proteins has been reviewed by Visser (1981). 

Hydrophobic amino acids have side chains that contain aliphatic groups (valine, leucine, and isoleucine) or aromatic groups (phenylalanine, tyrosine, and tryptophan) that may form hydrophobic interactions. 

Of the three aromatic amino acids phenylalanine, tyrosine and tryptophan, phenylalanine has been classified with the hydrophobic amino acids which have a non-polar side chain and tyrosine with those containing a hydroxyl group. This leaves tryptophan, the largest and rarest of the amino acids which contains the heterocyclic indole nucleus as its bulky R group. Trytophan is the parent compound for the neurotransmitter serotonin which is 5-hydroxytryptamine. 

The structures of the 20 primary amino acids are given in Figure 1. Amino acids are divided into hydrophobic and hydrophilic residues. The first group includes those with aliphatic side chains (Ala, Val, lie. Leu, Met) and those with aromatic side chains (Phe, Tyr, Trp). The hydrophilic group includes amino acids with neutral, polar side chains (Ser, Thr, Asn, Gin), those with acidic (Asp and Glu) or with basic side chains as Lys, Arg and His. 

In polar solvents, the structure of the acridine 13 involves some zwitterionic character 13 a [Eq. (7)] and the interior of the cleft becomes an intensely polar microenvironment. On the periphery of the molecule a heavy lipophilic coating is provided by the hydrocarbon skeleton and methyl groups. A third domain, the large, flat aromatic surface is exposed by the acridine spacer unit. This unusual combination of ionic, hydrophobic and stacking opportunities endows these molecules with the ability to interact with the zwitterionic forms of amino acids which exist at neutral pH 24). For example, the acridine diacids can extract zwitterionic phenylalanine from water into chloroform, andNMR evidence indicates the formation of 2 1 complexes 39 such as were previously described for other P-phenyl-ethylammonium salts. Similar behavior is seen with tryptophan 40 and tyrosine methyl ether 41. The structures lacking well-placed aromatics such as leucine or methionine are not extracted to measureable degrees under these conditions. 

Aromatic side chains of amino acids such as phenylalanine, tryptophan, and tyrosine are found in general in the interior of proteins, in hydrophobic regions. In some proteins they mediate helix-helix contacts. It is to be expected that agents containing aromatic groups could interact with proteins via aromatic-aromatic interactions, as for instance, proven by X-ray studies of biphenyl compounds which inhibit sickle-cell hemoglobin gelation. 

Hydrocarbons (both aromatic and aliphatic) do not have many (or any) groups that can participate in the hydrogen-bonding network of water. They re greasy and prefer to be on the interior of proteins (away from water). Note that a couple of the aromatics, Tyr and Trp, have O and N, and Met has an S, but these amino acids are still pretty hydrophobic. The hydrophobic nature usually dominates however, the O, N, and S atoms often participate in hydrogen bonds in the interior of the protein. 

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