Tyrosine residue

Amino acid-derived hormones include the catecholamines, epinephrine and norepinephrine (qv), and the thyroid hormones, thyroxine and triiodothyronine (see Thyroid AND ANTITHYROID PREPARATIONS). Catecholamines are synthesized from the amino acid tyrosine by a series of enzymatic reactions that include hydroxylations, decarboxylations, and methylations. Thyroid hormones also are derived from tyrosine iodination of the tyrosine residues on a large protein backbone results in the production of active hormone. 

Thyroid Hormones. Iodine, absorbed as P, is oxidized in the thyroid and bound to a thyroglobulin. The resultant glycoprotein, mol wt 670,000, contains 120 tyrosine residues of which ca two-thirds are available for binding iodine in several ways. Proteolysis introduces the active hormones 3,5,3 -triiodothyronine (T ) and 3,5,3, 5 -tetraiodothyronine (T, (thyroxine) in the ratio Ty.T of 4 1 (121,122). 

In order for the cyclooxygenase to function, a source of hydroperoxide (R—O—O—H) appears to be required. The hydroperoxide oxidizes a heme prosthetic group at the peroxidase active site of PGH synthase. This in turn leads to the oxidation of a tyrosine residue producing a tyrosine radical which is apparendy involved in the abstraction of the 13-pro-(5)-hydrogen of AA (25). The cyclooxygenase is inactivated during catalysis by the nonproductive breakdown of an active enzyme intermediate. This suicide inactivation occurs, on average, every 1400 catalytic turnovers. 

Thiocyanate ion, SCN , inhibits formation of thyroid hormones by inhibiting the iodination of tyrosine residues in thyroglobufin by thyroid peroxidase. This ion is also responsible for the goitrogenic effect of cassava (manioc, tapioca). Cyanide, CN , is liberated by hydrolysis from the cyanogenic glucoside finamarin it contains, which in turn is biodetoxified to SCN. 

There are five known classes of enzyme-linked receptors (1) receptor tyrosine kinases, which phosphorylate specific tyrosine residues on intracellular signaling proteins (2) tyrosine kinase-associated receptors, such as the prolactin and growth hormone receptors we have already discussed, which... 

The polypeptide chain of Src tyrosine kinase, and related family members, comprises an N-terminal "unique" region, which directs membrane association and other as yet unknown functions, followed by a SH3 domain, a SH2 domain, and the two lobes of the protein kinase. Members of this family can be phosphorylated at two important tyrosine residues—one in the "activation loop" of the kinase domain (Tyr 419 in c-Src), the other in a short... 

Figure 13.30 Ribbon diagram of the structure of Src tyrosine kinase. The structure is divided in three units starting from the N-terminus an SH3 domain (green), an SH2 domain (blue), and a tyrosine kinase (orange) that is divided into two domains and has the same fold as the cyclin dependent kinase described in Chapter 6 (see Figure 6.16a). The linker region (red) between SH2 and the kinase is bound to SH3 in a polyproline helical conformation. A tyrosine residue in the carboxy tail of the kinase is phosphorylated and bound to SH2 in its phosphotyrosine-binding site. A disordered part of the activation segment in the kinase is dashed. (Adapted from W. Xu et al.. Nature 385 595-602, 1997.)...

PHOSPHOPROTEINS. These proteins have phosphate groups esterified to the hydroxyls of serine, threonine, or tyrosine residues. Casein, the major protein of milk, contains many phosphates and serves to bring essential phosphorus to the growing infant. Many key steps in metabolism are regulated between states of activity or inactivity, depending on the presence or absence of phosphate groups on proteins, as we shall see in Chapter 15. Glycogen phospho-rylase a is one well-studied example. 

The improvements in resolution achieved in each deconvolution step are shown in Figure 3-3. While the initial library could only afford a modest separation of DNB-glutamic acid, the library with proline in position 4 also separated DNP derivatives of alanine and aspartic acid, and further improvement in both resolution and the number of separable racemates was observed for peptides with hydrophobic amino acid residues in position 3. However, the most dramatic improvement and best selectivity were found for c(Arg-Lys-Tyr-Pro-Tyr-(3-Ala) (Scheme 3-2a) with the tyrosine residue at position 5 with a resolution factor as high as 28 observed for the separation of DNP-glutamic acid enantiomers. 

The cDNA for this photoprotein has been cloned and expressed in E. coli, and the recombinant protein obtained was named mitrocomin (Fagan et al., 1993). Mitrocomin consists of 190 amino acid residues with a tyrosine residue at the C-terminus, and has three Ca2+-binding sites. 

Phosphorylation is a common method of regulation. As described above, SH2 domains bind to phosphorylated tyrosine residues. Conversely, phosphorylation of serines and threonines proximal to SH3 and PDZ domains uncouples them from their target motifs. Therefore modulation of protein kinase activity in cells regulates interactions between adaptor proteins and their target proteins. 

Insulin Receptor. Figure 1 Structure and function of the insulin receptor. Binding of insulin to the a-subunits (yellow) leads to activation of the intracellular tyrosine kinase ((3-subunit) by autophosphorylation. The insulin receptor substrates (IRS) bind via a phospho-tyrosine binding domain to phosphorylated tyrosine residues in the juxtamembrane domain of the (3-subunit. The receptor tyrosine kinase then phosphorylates specific tyrosine motifs (YMxM) within the IRS. These tyrosine phosphorylated motifs serve as docking sites for some adaptor proteins with SRC homology 2 (SH2) domains like the regulatory subunit of PI 3-kinase. 

MAPK cascades are composed of three cytoplasmic kinases, the MAPKKK, MAPKK, and MAPK, that are regulated by phosphorylation (Fig. 1) [1, 2]. The MAPKKK, also called MEKK for MEK kinase, is a serine/threonine kinase. Selective activation of MAPKKKs by upstream cellular stimuli results in the phosphorylation of MAPKK, also called MEK for MAP/ERK kinase by the MAPKKK. MAPKKK members are structurally diverse and are differentially regulated by specific upstream stimuli. The MAPKK is phosphorylated by the MAPKKK on two specific serine/ threonine residues in its activation loop. The MAPKK family members are dual specificity kinases capable of phosphorylating critical threonine and tyrosine residues in the activation loop of the MAPKs. MAPKKs have the fewest members in the MAPK signaling module. MAPKs are a family of serine/threonine kinases that upon activation by their respective MAPKKs, are capable of phosphorylating cytoplasmic substrates as well as... 

Neuropeptide Y (NPY) is a 36 amino acid polypqrtide with tyrosine residues at both ends of the molecule. It is characterised structurally by a PP-fold consisting of an extended polyproline helix and an a-helix connected by a (3-tum [1]. Based on structural and evolutionary criteria, NPY is closely related to peptide YY (PYY) and pancreatic polypeptide (PP). 

Phosphorylation is the reversible process of introducing a phosphate group onto a protein. Phosphorylation occurs on the hydroxyamino acids serine and threonine or on tyrosine residues targeted by Ser/Thr kinases and tyrosine kinases respectively. Dephosphorylation is catalyzed by phosphatases. Phosphorylation is a key mechanism for rapid posttranslational modulation of protein function. It is widely exploited in cellular processes to control various aspects of cell signaling, cell proliferation, cell differentiation, cell survival, cell metabolism, cell motility, and gene transcription. 

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