Tyrosine, posttranslational processing

Reversible phosphorylation requiring both a kinase and a phosphatase is implicated in the control of many cellular process. Generally, a phosphate group is linked to serine or threonine and also to tyrosine residues in proteins. Phosphorylation in enzyme molecules generally leads to a modification of the catalytic activity (see review, England, 1980). Other modifications have been also described such as methylations and ADP-ribosylation. Formation of disulfide bonds is also a posttranslational process. 

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. 

One of the most fascinating questions concerning these enzymes is the mechanism of oxidation of the active-site tyrosine residue to form TPQ. This is a posttranslational, self-processing, six-electron oxidation that requires only the apo protein, Cu(ll), and 20i per TPQ. The sttuctures... 

The reversible phosphorylation of proteins is one of the most widespread posttranslational modifications, mediating responses to internal and external signals in a variety of cellular processes [1-3]. In eukaryotes 30-70 % of all proteins are phosphorylated on tyrosine (Tyr), threonine (Thr), and/or serine (Ser) residues [4-6]. Protein phosphorylation is catalyzed by protein kinases, which transfer the y-phosphate of ATP to a hydroxyl side chain, resulting in the formation of a phosphate monoester. Protein phosphatases hydrolyze these phosphate monoesters and make protein phosphorylation a reversible modification [4]. 

Reversible phosphorylation of proteins on serine, threonine and tyrosine residues by protein kinases and phosphatases represents the principal mechanism of signal transduction events that control a multitude of cellular processes (see ref. 1 and 2 for detained reviews). Phosphorylation is a posttranslational chemical modification that is used by prokaryotic and eukaryotic cells to define the properties of a large... 

Many other amino acids, in addition to the ones listed here, are known to exist. They occur in some, but by no means all, proteins. Figure 3.4 shows some examples of the many possibilities. They are derived from the common amino acids and are produced by modification of the parent amino acid after the protein is synthesized by the organism in a process called posttranslational modification. Hydroxyproline and hydroxylysine differ Ifom the parent amino acids in that they have hydroxyl groups on their side chains they are found only in a few connective-tissue proteins, such as collagen. Thyroxine differs from tyrosine in that it has an extra iodine-containing aromatic group on the side... 

The TPQ moiety is derived from a tyrosine in the active site of CAO, through posttranslational modification (103). This biogenesis of TPQ is a self-catalytic process, requiring only the active site Cu(II) and dio gen (104). 

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