Phosphoryl transferases

Vanadium. Vanadium is essential in rats and chicks (85,156). Estimated human intake is less than 4 mg/d. In animals, deficiency results in impaired growth, reproduction, and Hpid metaboHsm (157), and altered thyroid peroxidase activities (112). The levels of coen2yme A and coen2yme Q q in rats are reduced and monoamine oxidase activity is increased when rats are given excess vanadium (157). Vanadium may play a role in the regulation of (NaK)—ATPase, phosphoryl transferases, adenylate cyclase, and protein kinases (112). 

In contrast to the other three cations, Mg2+ has a much slower exchange rate of water in its hydration sphere (Table 10.1). Mg2+ often participates in structures, for example in ATP-binding catalytic pockets of kinases and other phosphoryl-transferase enzymes, where... 

Unlike the other alkaline earth and transition metal ions, essentially on account of its small ionic radius and consequent high electron density, Mg2+ tends to bind the smaller water molecules rather than bulkier ligands in the inner coordination sphere. Many Mg2+-binding sites in proteins have only 3, 4 or even less direct binding contacts to the protein, leaving several sites in the inner coordination sphere occupied by water, or in the phosphoryl transferases, by nucleoside di- or triphosphates. 

Class 2. Transferases transfer chemical groups from one molecule to another, or within a single molecule. They include amino, acyl, methyl, glucosyl, and phosphoryl transferases, kinases, phosphomutases, transaldolase, and transketolase. 

IV), and 1,3,5-triazine derivatives, (V), prepared by Armistead (5) and Bebbington (6), respectively, were effective as phosphoryl transferase inhibitors and used in the treatment of cardiovascular diseases. 

The three tissue enzymes known to participate in formation of the phosphate esters are (1) thiaminokinase (a pyro-phosphokinase), which catalyzes formation of TPP and adenosine monophosphate (AMP) from thiamine and adenosine triphosphate (ATP) (2) TPP-ATP phosphoryl-transferase (cytosoHc 5"-adenylic kinase)which forms the triphosphate and adenosine diphosphate from TPP and ATP and (3) thiamine triphosphatase, which hydrolyzes TPP to the monophosphate. Although thiaminokinase is widespread, the phosphoryl transferase and membrane-associated triphosphatase are mainly in nervous tissue. 

In contrast to the other three cations, Mg has a much slower exchange rate of water in its hydration sphere (Table 10.1). Mg often participates in structures, for example, in ATP binding catalytic pockets of kinases and other phosphoryl transferase enzymes, where the metal is bound to four or five ligands from the protein and the ATP. This leaves one or two coordination positions vacant for occupation by water molecules, which can be positioned in a particular geometry by the Mg to participate in the catalytic mechanism of the enzyme. This capacity is an example of outer sphere activation of a substrate by a metal ion (Figure 10.1) as distinct from the... 

Although named after a dehalogenase, of the more than 3000 sequenced proteins of the HAD family, the vast majority are phosphoryl transferases. 

In these studies of phosphoryl transferases, new structural information is provided, which x jay for the most part has not provided or, at any rate, not yet. This is clearly a healthy sign for the employment of NMR. For most protein NMR work that has appeared so far, the final product of the experiment has been a comparison of a very limited number of distance parameters to the corresponding values obtained from the x-ray structure. This is acceptable in the testing stages of the NMR methods, but clearly the correctness and reasonableness of the NMR structural conclusions may be substantially aided by the fact that the investigator can, so to speak, look up the answer in the back of the book. One hopes (and in general believes) that the investigator s intellectual honesty will impel him to report discrepancies, for such discrepancies may well be real. 

Tada, K., Takeda, G., Omura, K. and Itokawa, Y. (1978), Congenital lactic acidosis due to pyruvate carboxylase deficiency. Absence of an inhibitor of TPP-ATP phosphoryl transferase. Eur. J. Pediatr., 127,141. 

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