Serine phosphate group attachment

PTEN is a phosphatase, which is a product of a tumor suppressor gene. This phosphatase has an unusual broad specificity and can remove phosphate groups attached to serine, threonine, and tyrosine residues. It is believed that its ability to dephosphorylate phosphati-dylinositol (PI) 3,4,5-triphosphate, the product of PI-3 kinase, is responsible for its tumor suppressor effects. 

Like virtually all intracellular signaling events, phosphorylation by PT3 kinase is reversible. The relevant phosphatase, termed PTEN phosphatase, has an unusually broad specificity. Although PTEN can remove phosphate groups attached to serine, threonine, and tyrosine residues in proteins, its ability to remove the 3-phosphate from PI 3,4,5-trisphosphate is thought to be its major function in cells. Overexpression of PTEN in cultured mammalian cells promotes apoptosis by reducing the level of PI 3,4,5-trisphosphate and hence the activation and anti-apoptotic effect of protein kinase B. 

These are the most common class of complex lipid (Figure 12.11) and contain a phosphoric acid residue (phosphate group) and two fatty acids esterified to glycerol. Attached to the phosphate group is an amino alcohol, sometimes referred to as the nitrogenous base, which may be either serine, choline or ethanolamine or sometimes the monomethyl or dimethyl derivatives of ethanolamine (Table 12.4). Alternatively, a polyhydroxy compound which is either glycerol, myo-inositol or one of their derivatives is attached instead... 

Eukaryotic phospholipids typically have two fatty acid chains linked to a glycerol by ester bonds, with the third position of the glycerol esterified to a phosphate group. Most phospholipids also have a head group such as choline, ethanolamine, or serine attached to the phosphate, and one such lipid is shown below (1-palmitoyl, 2-oleoyl phosphatidylcholine). The precise function of the variable head groups has not yet been established. 

Figure 1.5 A phospholipid molecule. In a phospholipid molecule, one fatty acid is replaced with a phosphate group, to which is attached (X) a nitrogen-containing molecule, for example choline, ethanolamine, serine or inositol (giving the phospholipid phosphatidylcholine, phos-phatidylethanolamine, phosphatidylserine or phosphatidylinositol, respectively).

In an attempt to determine the points of attachment of the pepsin-phosphorus, Flavin succeeded in the isolation of three peptides Thr.SerP SerP.Glu and Thr.(Glu, SerP) (22). This evidence indicates that the single phosphate group of this protein is esterified in part to a serine residue. Moreover, the amino acid sequence Thr.SerP.Glu represents the third example in which the phosphoserine residue in a phosphoprotein is linked to a dicarboxylic acid. The second point of attachment of this phosphate diester, however, is still unknown. 

CE Family 1 is very large and contains members which do not act on carbohydrate-derived substrates. The crystal structure of a CE 1 domain of XynlOB modular enzyme from Clostridium thermocellum has been solved. " The CE 1 domain is a feruloyl esterase which hydrolyses the feruloyl groups attached to some arabinofuranosyl 05 groups in native xylan. (The Xyn lOB protein as a whole consists of two CBM 22 domains, a dockerin domain, and a GH 20 xylanase domain, and forms part of a cellulosome - see Section 5.10.) The enzyme has the common a/p hydrolase fold. Studies of ferulic acid complexes of the inactive alanine mutant of the active site serine revealed the classic catalytic triad, and two main-chain peptide NH bonds are in place to form an oxyanion hole . A remarkable feature is that the enzyme as repeatedly isolated was esterilied on the active site serine by phosphate or sulfate. 

Synthesis of glucose-l-phosphate. Glucose-6-phosphate is reversibly converted to glucose-l-phosphate by phosphoglucomutase, an enzyme that contains a phosphoryl group attached to a reactive serine residue ... 

The enzyme s phosphoryl group is transferred to glucose-6-phosphate, forming glucose-1,6-bisphosphate. As glucose-l-phosphate forms, the phosphoryl group attached to C-6 is transferred to the enzyme s serine residue. 

The half-lives and the corresponding k+3 values are dependent on the structure of, and therefore the source of, the enzyme and the structure of the group attached to the serine residue of the enzyme. Note the tremendous difference between the acetylated enzyme and the enzyme s phosphate and carbamate adducts. The half-lives are generally lower for the carbamylated enzymes but long enough to cause serious poisoning. 

F. 393. Pyridoxal phosphate covalently attached to an amino acid substrate. The arrows indicate which bonds are broken for the various typies of reactions in which pyridoxal phosphate is involved. The X and Y represent leaving groups that may be present on the amino acid (such as the hydroxyl group on serine or threonine). 

Phosphorylation, principally on serine, threonine, or tyrosine residues, is one of the most important and abundant post-translational modifications (PTMs), with more than 30% of proteins being modified by the covalent attachment of one or more phosphate groups. It plays a critical role in the regulation of various cellular processes including cell cycle, growth, apoptosis, and transmitting extracellular signals to the nucleus. In fact, protein phosphorylation is... 

The most abundant phosphoglycerides have one of the alcohols choline, ethanolamine, or serine attached to the phosphate group. These aminoalcohols are shown below in charged forms ... 

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