Isoleucine relative hydrophobicity

As noted by the original authors (Dorovska et al., 1972), and cited by Fersht (1985), there is an excellent linear correlation between log/ccat/KM and the Hansch hydrophobicity parameters (v) of the side chains (Fig. 9, A), except for the two branched side chains (valine and isoleucine residues). However, since the ku values for the esters do vary somewhat (Table A6.8), the values of pKrs do not correlate as strongly with ir (Fig. 9, B). Moreover, the plot shows distinct curvature which probably indicates the onset of a saturation effect due to the physical limits of the Sj binding pocket, adjacent to the enzyme s active site. Still, the points for valine and isoleucine deviate below the others, suggesting that the pocket has a relatively narrow opening. 

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). 

Irreversible insolubilization of proteins may occur mainly through formation of both intermolecular disulfide and hydrophobic bonds. The product can be quite different depending on the relative contribution of these two types of bonds. The hydrophobic bonds are formed among the hydrophobic amino acid side chains contributed by valine, leucine, isoleucine, phenylalanine, etc. 

COX-1 and COX-2 are of similar molecular mass (approximately 70 and 72 kDa respectively), with 65% amino acid sequence homology and near-identical catalytic sites. The most significant difference between the isoenzymes, which allows for selective inhibition, is the substitution of isoleucine at position 523 in COX-1 with valine in COX-2. The relatively smaller Val523 residue in COX-2 allows access to a hydrophobic side-pocket in the enzyme (which Ile523 sterically hinders). Drugs, such as the coxibs, bind to this alternative site and are considered to be selective inhibitors of COX-2. 

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... 

For assembly of novel three-dimensional (3D) structures, block copolypeptides are required that have structural domains (i.e., amino acid sequences) whose size and composition can be precisely adjusted. Such materials have proven elusive using conventional techniques. Strong base-initiated NCA polymerizations are very fast. These polymerizations are poorly understood and well-defined block copolymers cannot be prepared. Primary amine-initiated NCA polymerizations are also not free of side reactions. Even after fractionation of the crude preparations, the resulting polypeptides are relatively ill-defined, which may complicate unequivocal evaluation of their properties and potential applications. Nevertheless, there are many reports on the preparation of block copolypeptides using conventional primary amine initiators. Examples include many hydrophilic-hydrophobic and hydrophilic-hydrophobic-hydrophilic di- and triblock copolypeptides (where hydrophilic residues were glutamate and lysine, and hydrophobic residues were leucine, valine, isoleucine, phenylalanine, and alanine" ) prepared to study... 

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