Phosphoryl group

A good example of an affinity label for creatine kinase has been presented (35). This enzyme catalyzes the reversible transfer of a phosphoryl group from adenosine triphosphate [56-65-5] (17) to creatine [57-00-1] (18), leading to adenosine diphosphate [7584-99-8] (19) and phosphocreatine [67-07-2]... 

FIGURE 3.8 The activation energies for phosphoryl group-transfer reactions (200 to 400 kj/mol) are substantially larger than the free energy of hydrolysis of ATP ( — 30.5 kj/mol). 

The concepts of destabilization of reactants and stabilization of products described for pyrophosphate also apply for ATP and other phosphoric anhydrides (Figure 3.11). ATP and ADP are destabilized relative to the hydrolysis products by electrostatic repulsion, competing resonance, and entropy. AMP, on the other hand, is a phosphate ester (not an anhydride) possessing only a single phosphoryl group and is not markedly different from the product inorganic phosphate in terms of electrostatic repulsion and resonance stabilization. Thus, the AG° for hydrolysis of AMP is much smaller than the corresponding values for ATP and ADP. 

FIGURE 10.27 The path of the phosphoryl group through the PTS mechanism. Reactive phosphohistidine intermediates of Enzyme I, HPr, and Enzyme III transfer phosphoryl groups from PEP to the transported sugar. 

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. 

The remaining steps in the glycolytic pathway prepare for synthesis of the second ATP equivalent. This begins with the phosphoglycerate mutase reaction (Eigure 19.23), in which the phosphoryl group of 3-phosphoglycerate is moved... 

A different mechanism operates in the wheat germ enzyme. 2,3-Bisphosphoglycerate is not a cofactor. Instead, the enzyme carries out intra-molecular phosphoryl group transfer (Figure 19.25). The C-3 phosphate is transferred to an active-site residue and then to the C-2 position of the original substrate molecule to form the product, 2-phosphoglycerate. 

The second ATP-synthesizing reaction of glycolysis is catalyzed by pyruvate kinase, which brings the pathway at last to its pyruvate branch point. Pyruvate kinase mediates the transfer of a phosphoryl group from phosphoenolpyru-vate to ADP to make ATP and pyruvate (Figure 19.27). The reaction requires... 

Pyruvate kinase possesses allosteric sites for numerous effectors. It is activated by AMP and fructose-1,6-bisphosphate and inhibited by ATP, acetyl-CoA, and alanine. (Note that alanine is the a-amino acid counterpart of the a-keto acid, pyruvate.) Furthermore, liver pyruvate kinase is regulated by covalent modification. Flormones such as glucagon activate a cAMP-dependent protein kinase, which transfers a phosphoryl group from ATP to the enzyme. The phos-phorylated form of pyruvate kinase is more strongly inhibited by ATP and alanine and has a higher for PEP, so that, in the presence of physiological levels of PEP, the enzyme is inactive. Then PEP is used as a substrate for glucose synthesis in the pathway (to be described in Chapter 23), instead... 

FIGURE 19.29 A mechanism for the pyruvate kinase reaction, based on NMR and EPR studies by Albert Mildvan and colleagues. Phosphoryl transfer from phosphoenolpyrnvate (PEP) to ADP occurs in four steps (a) a water on the Mg ion coordinated to ADP is replaced by the phosphoryl group of PEP (b) Mg dissociates from the -P of ADP (c) the phosphoryl group is transferred and (d) the enolate of pyruvate is protonated. (Adapted from Mildvan, A., 1979. Advances in Eiizymology 49 103-126.)... 

The mechanism of succinyl-CoA synthetase is postulated to involve displacement of CoA by phosphate, forming succinyl phosphate at the active site, followed by transfer of the phosphoryl group to an active-site histidine (making a phosphohistidine intermediate) and release of succinate. The phosphoryl moiety is then transferred to GDP to form GTP (Figure 20.13). This sequence of steps preserves the energy of the thioester bond of succinyl-CoA in a series of high-energy intermediates that lead to a molecule of ATP ... 

The IV-phosphoryl group in azoxyfurazan 233 was removed under basic conditions (MeOH/KOH, -30°C) to give a mixture of azo compounds 234 and 235, albeit in low yield (Scheme 158) (93IZV609, 93RCB577). 

Transfer of the phosphoryl group to ADP in step 10 then generates ATP and gives enolpyruvate, which undergoes tautomerization to pyruvate. The reaction is catalyzed by pyruvate kinase and requires that a molecule of fructose 1,6-bis-phosphate also be present, as well as 2 equivalents of Mg2+. One Mg2+ ion coordinates to ADP, and the other increases the acidity of a water molecule necessary for protonation of the enolate ion. 

O -. - which is isomerized by transfer of the phosphoryl group to give 3-phospho-glycerate. 

These phosphorus-containing PAN derivatives are unstable under hydrolytic conditions, and the phosphoryl groups are easily split off under the action of boiling water. If, however, the modified PAN is treated with dimethyl phosphite solution in toluene in the presence of dimethylamine, a modified PAN, stable towards hydrolysis, is obtained. Its composition seems to be the following ... 

An early observation that 2 -d-3 -AMP was a more potent inhibitor of adenylyl cyclases than 2 -d-Ado suggested that the enzyme would accept substitutions at the 3 -ribose position and that phosphate was particularly well tolerated. This led to the generation of a family of 3 -phosphoryl derivatives of 2, 5 -dideoxyadenosine exhibiting ever greater inhibition with the addition of an increasing number of 3 -phosphoryl groups, the most potent of which is 2, 5 -dideoxyadenosine-3 -tetraphosphate (2, 5 -dd-3 -A4P Table 4) [5]. These constitute a class of inhibitors historically referred to as P -site ligands that caused inhibition of adenylyl... 

Histone phosphorylation is a common posttranslational modification fond in histones, primarily on the N-terminal tails. Phosphorylation sites include serine and threonine residues, tyrosine phosphorylation has not been observed so far. Some phosphorylation events occur locally whereas others occur globally throughout all chromosomes during specific events like mitosis. Histone phosphorylation is catalyzed by kinases. Removal of the phosphoryl groups is catalyzed by phosphatases. 

Enzyme that catalyses the transfer of the y-phosphoryl group of ATP to acceptor hydroxyl groups of serine, threonine and tyrosine residues in the protein. 

II cleaves the two complementary strands of DNA four base pairs apart and the resulting 5 -phosphoryl groups become covalently linked to a pair of tyrosine groups, one in each half of the dimeric topoisomerase II enzyme. Several groups of drugs are known that selectively inhibit topoisomerases in bacteria (quino-lones) or mammalian cells (etoposide, tenoposide). Quinolones are used to treat bacterial infections inhibitors of mammalian topoisomerases are cytostatic drugs used for the treatment of cancer. 

We have studied the extractant behavior of a series of compounds containing the carbamoylmethylphosphoryl (CMP) moiety in which the basicity of the phosphoryl group and the steric bulk of the substituent group are varied (10,LL). These studies have led to the development of extractants which have combinations of substituent groups that impart to the resultant molecule improved ability to extract Am(III) from nitric acid and to withstand hydrolytic degradation. At the same time good selectivity of actinides over most fission products and favorable solubility properties on actinide loading are maintained (11). 

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