Phosphorylation of protein side chains

Photosynthetic phosphorylation of protein side chains 79 substrate level 775, 800 Phosphorylation, photosynthetic. See Photosynthetic phosphorylation Phosphorylation reactions 303 Phosphorylation state ratio definition of 303 O-Phosphoserine 610s Phosphoserine 545 Phosphothreonine 545 Phosphotransferase system bacterial 419,420 Phosphotransferases 637... 

Insulin stimulates the phosphorylation of serine side chains of many proteins, including ATP citratelyase, acetyl-CoA carboxylase, and ribosomal subunit S6. 

The binding of a hormone or growth factor (a ligand) to a dimeric receptor activates the protein kinase domain of the receptor which phosphorylates a number of tyrosine hydroxyl groups of the receptor itself. This autophosphorylation is followed by a variety of events, which include phosphorylation of tyrosine side chains of various other proteins.426 An-... 

As we shall see, transductions of all six types commonly require the activation of protein kinases, enzymes that transfer a phosphoryl group from ATP to a protein side chain. 

Proteins are made of twenty standard amino acid residues joined together through peptide bonds. Each of the twenty amino acids has unique physico-chemical properties stemming from the size of the side chain, and the possible presence of an acidic or basic ionizable group. Protein phosphorylation most... 

Phosphoproteins.— Details of the amino-acid sequences at the phosphorylation sites of two proteins involved in glycogen metabolism have been published, and they show unusual features. For example, there is an unusually high proportion of hydroxyl side-chains near the phosphoserine at one of the phosphorylation sites in glycogen synthetase, ... 

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]. 

The use of QM-MD as opposed to QM-MM minimization techniques is computationally intensive and thus precluded the use of an ab initio or density functional method for the quantum region. This study was performed with an AMi Hamiltonian, and the first step of the dephosphorylation reaction was studied (see Fig. 4). Because of the important role that phosphorus has in biological systems [62], phosphatase reactions have been studied extensively [63]. From experimental data it is believed that Cys-i2 and Asp-i29 residues are involved in the first step of the dephosphorylation reaction of BPTP [64,65]. Alaliambra et al. [30] included the side chains of the phosphorylated tyrosine, Cys-i2, and Asp-i 29 in the quantum region, with link atoms used at the quantum/classical boundaries. In this study the protein was not truncated and was surrounded with a 24 A radius sphere of water molecules. Stochastic boundary methods were applied [66]. 

FIGURE 15.2 Enzymes regulated by covalent modification are called interconvertible enzymes. The enzymes protein kinase and protein phosphatase, in the example shown here) catalyzing the conversion of the interconvertible enzyme between its two forms are called converter enzymes. In this example, the free enzyme form is catalytically active, whereas the phosphoryl-enzyme form represents an inactive state. The —OH on the interconvertible enzyme represents an —OH group on a specific amino acid side chain in the protein (for example, a particular Ser residue) capable of accepting the phosphoryl group. 

Evolution has provided the cell with a repertoire of 20 amino acids to build proteins. The diversity of amino acid side chain properties is enormous, yet many additional functional groups have been selectively chosen to be covalently attached to side chains and this further increases the unique properties of proteins. Diese additional groups play a regulatory role allowing the cell to respond to changing cellular conditions and events. Known covalent modifications of proteins now include phosphorylation, methylation, acetylation, ubi-quitylation, hydroxylation, uridylylation and glycosyl-ation, among many others. Intense study in this field has shown the addition of a phosphate moiety to a protein... 

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