Tyrosine relative hydrophobicity

The results of kinetic and X-ray crystallographic experiments on mutant carbonic anhydrases II, in which side-chain alterations have been made at the residue comprising the base of the hydrophobic pocket (Val-143), illuminate the role of this pocket in enzyme-substrate association. Site-specific mutants in which smaller hydrophobic amino acids such as glycine, or slightly larger hydrophobic residues such as leucine or isoleucine, are substituted for Val-143 do not exhibit an appreciable change in CO2 hydrase activity relative to the wild-type enzyme however, a substitution to the bulky aromatic side chain of phenylalanine diminishes activity by a factor of about 10 , and a substitution to tyrosine results in a protein which displays activity diminished by a factor of about 10 (Fierke et o/., 1991). 

Aromatic R Groups Phenylalanine, tyrosine, and tryptophan, with their aromatic side chains, are relatively nonpolar (hydrophobic). All can participate in hydrophobic interactions. The hydroxyl group of tyrosine can form hydrogen bonds, and it is an important func-... 

A more extensive study of mobilities of 3H- and 14C-labeled amino acids again found that amino acids labeled with 14C at Cl or C2 are retained on the column, relative to the unlabeled forms.135 Lysine is an exception. Tritiation at C3 also increases the retention time, but tritiation at C2 of glycine or at C4, C5, or C6 of lysine decreases it, and large decreases are seen with methionine tritium-labeled in the methyl and with tyrosine tritium-labeled at C3, 5. The 14C IEs can be attributed to a decrease of acidity, but the IEs of distant 3H may be due to hydrophobic interactions with the resin. A remarkable result is that intramolecular isotopic isomers (isotopomers) can be distinguished on the basis of their chromatographic mobilities. 

Effects of amino acids The effects of 18 kinds of amino acids on crystal appearance are summarized in table 4. Among these amino acids tested, only leucine and tryptophan affected the change in crystal form from pillars to thin plates at concentrations relative to Lmore than 3%. These two amino acids are hydrophobic, so they might interact with the Lrphenylalanine skeleton in the crystal structure of di-L-phenylalanine sulfate monohydrate and are supposed to suppress growth in the a-axis direction. Isoleucine, valine and tyrosine which are analogous... 

The reactivity of amino acids within a protein actually can vary considerably with regard to their reactivity for labeling due to variations in the microenvironment of the residues. These differences in reactivity are related to a number of factors including proximity to hydrophobic sequences or bulky amino acids such as tryptophan. Accessibility to solvent also must be considered. The relative amino acid reactivity of amino adds toward labeling has not been investigated on mAbs because of their complexity. However, studies with smaller proteins and peptides have documented, for example, that the rate of iodination of tyrosine residues in these molecules can vary by factors of 50-100 (Dube et al. 1966 Seon et al. 1970). 

In addition to the specific interactions described above, there is an important hydrophobic S2 binding site which accommodates the P2-proline residue. The number of non-bonded contacts made by atoms of the proline ring with atoms of this S2 binding site is relatively small - twelve compared to more than forty for the P2-tyrosine. The S3 binding site is formed by the two main chain hydrogen bonds from P3Ala (the NH and CO) to Gly 216 (CO-NH) in an approximately antiparallel sheet. 

Several other conserved amino acid residues are found in the vicinity of the conserved central His residue in both the a and yS-polypeptides. There is usually a leucine (a-polypeptide) or large aromatic residue (fi-polypeptide) located at His +4 (numbered relative to the conserved His, considered as position 0) and, located about one or-helix turn away at His -4, a small hydrophobic residue (Brunisholz et al., 1984 Theiler Zuber, 1984). Conserved tyrosine or tryptophan residues are found at positions His +4, +6 and +9 in the LHl, or His +9 in the LH2 yS-poly-peptides and at position His +11 in the LHl and His +9 and +14 in the LH2 -polypeptides (Zuber Cogdell, 1995). These aromatic amino acid residues create a particular microenvironment for the His-bound Bchl molecules, thereby influencing their spectral characteristics (Fowler et al., 1992 Sturgis et al., 1995). The structures of the LH2 and RC-LHl complexes are described in detail below. 

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