The Hydroxyl Group of Tyrosine

FIGURE 6.7 (A) Rearrangement to the substituted phenol during acidolytic debenzylation of O-benzyltyrosine. Alkylation also occurs by intermolecular reaction. (B) Alkylation does not occur during acidolysis of 2-bromobenzyloxycarbonyltyrosine. The oxycarbonylphenol produced is a weaker nucleophile than phenol, and the cation that is generated is farther away from the nucleophile. 

BW Erickson, RB Merrifield. Acid stability of benzylic protecting groups used in solid-phase peptide synthesis. Rearrangement of O-benzyltyrosine to 3-benzylty-rosine. J Am Chem Soc 95, 3750, 1970. 

D Yamashiro, CH Li. Protection of tyrosine in solid-phase synthesis. (BrZ) J Org Chem 38, 591, 1973. 

M Englehard, RB Merrifield. Tyrosine protecting groups. Minimization of rearrangement to 3-alkyltyrosine during acidolysis. (O-cyclohexyltyrosine) J Am Chem Soc 100, 3559, 1978. 

K Rosenthal, A Karlstrom, A Unden. The 2,4-dimethylpent-3-yloxycarbonyl (Doc) group as a new nucleophile-resistant protecting group for tyrosine in solid phase peptide synthesis. Tetrahedron Lett 38, 1075, 1997. 

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FIGURE 24-2 Tyrosine phosphorylation and dephosphorylation. Protein tyrosine kinases (PTK) catalyze the transfer of the y-phosphate group from ATP to the hydroxyl group of tyrosine residues, whereas protein tyrosine phosphatases (PTP) remove the phosphate group from phosphotyro-sine. R, protein. 

Sulfation in most aspects is very similar to phosphorylation, except that sulfation is not involved in intracellular signal transduction, but in other forms of signaling. The mechanism of sulfation is similar to that of phosphorylation as a general base from the enzyme active site that deprotonates the hydroxyl groups of tyrosine residues. The nucleophilic oxygen then attacks the /3-position, in contrast to the 7-position in phosphorylation, and releases adenosine 3, 5 -diphosphate. 

The aromatic amino acids, phenylalanine, tyrosine, and tryptophan, have ring structures and are nonpolar with the exception of the hydroxyl group of tyrosine. 

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-... 

Denaturation. Proteins are quite susceptible to denaturation in alkaline solution because of decreased stabilization of the tertiary structure by elimination of electrostatic interactions between carboxylate and protonated amino and guanidinium groupings (Equations 1 and 2) and hydrogen bonding between the hydroxyl group of tyrosine and carboxylate groups (Equation 3). 

Formation of retinoyl CoA, followed by formation of an ester with the hydroxyl group of tyrosine, threonine or serine, or a thio-ester with the sutfhydryl group of cysteine (Figure 2.7). The source of retinoic acid for... 

Phenol serves as a basic unit of larger molecules, e.g. tyrosine residues in proteins. The phenoxyl radical is treated as a model system for the tyrosyl radical whose formation via abstraction of the hydrogen atom from the hydroxyl group of tyrosine is a typical feature of oxidative stress in the physiological pH range -... 

Many hormones, such as epinephrine (adrenaline), alter the activities of enzymes by stimulating the phosphorylation of the hydroxyl amino acids serine and threonine phosphoserine and phosphothreonine are the most ubiquitous modified amino acids in proteins. Growth factors such as insulin act by triggering the phosphorylation of the hydroxyl group of tyrosine residues to form phosphotyrosine. The phosphoryl groups on these three modified amino acids are readily removed thus they are able to act as reversible switches in regulating cellular processes. The roles of phosphorylation in signal transduction will be discussed extensively in Chapter 14. 

Each p subunit consists primarily of a protein kinase domain, homologous to protein kinase A. This kinase differs from protein kinase A in two important ways. First, the insulin receptor kinase is a tyrosine kinase that is, it catalyzes the transfer of a phosphoryl group from ATP to the hydroxyl group of tyrosine, rather than serine or threonine, as is the case for protein kinase A. 

V-M-Y-Y-E-N This is the single-letter amino acid abbreviation for a peptide. Draw the structure of this peptide. What is the net charge of this peptide at pH 7.0 An enzyme called a protein tyrosine kinase can attach phosphates to the hydroxyl groups of tyrosine. What is the net charge of the peptide at pH 7.0 after it has been phosphorylated by a tyrosine kinase What is the likely source of phosphate utilized by the kinase for this reaction ... 

An oligonucleotide bearing a 3 -phosphoryltyrosine residue has been synthesised from the modified tentagel or controlled pore glass solid support (202). The hydroxyl group of tyrosine was protected with a levulinoyl group which could be removed with sodium borohydride. 

Tyrosine or phenylalanine residues in position 2 are essential for activity. Replacement of the aromatic amino acid by serine inactivates the hormone completely. The phenylalanine derivative is less active than the tyrosine derivative, indicating that the hydroxyl group of tyrosine, although not essential, enhances the hormonal activity. 

Isothiocyanates also react with the hydroxyl group of tyrosine and other hydroxyamino acids. The addition of a hydroxy compound usually yields N-substituted thiocarbamates, which are esters of AT-substituted thiocarbamoic acids (Figure 2.67). 

The three members of the aromatic R group are phenylalanine, tyrosine and tryptophan (Figure 3.12). Phenylalanine is the leastpolar of the three. The hydroxyl group of tyrosine is an important functional group for hydrogen bonding in some enzymes. 

Mutagenesis of B/Lee/40 NA based on the crystal structure revealed the critical role of the hydroxyl group of tyrosine 409, positioned to interact with the positively charged C2 carbon postulated in the carbocation intermediate. Conservative substitution of phenylalanine at this position yielded enzyme that was correctly folded... 

Krysteva et aL (1973) have studied the environment of the most exposed tyrosine of chicken ovomucoid. The glycoprotein was treated with tetranitro me thane, and the nitrotyrosine peptide was isolated from the degraded fragments. The peptide which contained neither neutral sugar nor glucosamine was positive for sialic acid. The authors proposed that the sialic acid residue was linked to the hydroxyl group of tyrosine as an 0-glycoside. 

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