Thio kinase

Acyl adenylate intermediates seem the general rule for acyl activation, but alternate mechanisms are known. An example is the succinyl thio-kinase reaction. The mammalian enzyme system utilizes guanosine triphosphate (GTP) or inosine triphosphate (ITP), although similar ATP-requiring enzymes are known from plants and bacteria. In addition to the coenzyme A derivative, a nucleoside disphosphate and inorganic phosphate are produced. 

The subsequent cleavage of the thio-ester succinylCoA into succinate and coenzyme A by succinic acid-CoA ligase (succinyl CoA synthetase, succinic thiokinase) is strongly exergonic and is used to synthesize a phosphoric acid anhydride bond ( substrate level phosphorylation , see p. 124). However, it is not ATP that is produced here as is otherwise usually the case, but instead guanosine triphosphate (CTP). However, GTP can be converted into ATP by a nucleoside diphosphate kinase (not shown). 

Fig. 3.8.6 Spectrophotometric assays of complexes V, I III, II—III, and citrate synthase activity. DTNB Dithio-nitrobenzoic acid, LDH lactic dehydrogenase, ME medium E, MF medium F, MG medium G, MH medium H, PEP phosphoenol pyruvate, PK Pyruvate kinase, TNB thio-nitrobenzoic acid...

Key Words Guanosine-5 -0-(3-thio)triphosphate phosphorylation serotonin (5-hydroxytryptamine) G protein kinase receptor calmodulin phospholipase. 

Kim KS, Sack JS, Tokarski JS, Qian L, Chao ST, Leith L, Kelly YF, Misra RN, Hunt JT, Kimball SD, Humphreys WG, Wautlet BS, Mulheron JG, Webster KR. Thio- and oxoflavopiridols, cyclin-dependent kinase 1-selective inhibitors Synthesis and biological effects. J Med Chem 2000 43 4126-34. 

Thioguanine is similar to 6-mercaptopurine in its action. The most active form is 6-thio-GMP, which inhibits guanylate kinase and, at higher concentrations, IMP dehydrogenase. Thio-IMP and thio-GMP also inhibit PRPP amidotransferase. 

Among alkylating affinity labels, 8-[(4-bromo-2, 3-dioxobutyl)thio] ADP and -ATP (199 n = 2 or 3), formed by successive treatments of the corresponding 8-bromoadenosine phosphates with lithium hydrosulphide and 1, 4-dibromo-butanedione, have been used to label pyruvate kinase from rabbit muscle.355... 

Lorsch and Szostak started [5] from a specific ATP-binding RNA, which had previously been selected by affinity chromatography on ATP agarose, [4] and used it to evolve an ATP-dependent oligonucleotide kinase. [5] An RNA pool in which the central sequence of the ATP binder had been partly randomized was synthesized and was surrounded by three completely randomized sequences of a total of 100 bases (Fig. 1). This pool was incubated with ATP-y-S. RNAs onto which the y-thio-phosphate group of the ATP-y-S had been transferred could be separated from the rest... 

A recent report (129) on the utilization of the (R f) and (5),p) isomers of ADP(a-S) (a thio substituted ADP) by Mn substituted creatine kinase has shown that the enzyme binds the (/ )(p) substrate with the Mn bound to the O but, with the (5)(p) substrate, the enzyme bound form is predominantly coordinated via the sulfur atom. Both these complexes result in the... 

McKay, G.A. Wright, G.D. Catalytic mechanism of enterococcal kanamycin kinase (APH(3 )-nia) viscosity, thio, and solvent isotope effects support a Theorell-Chance mechanism. Biochemistry, 35, 8680-8685 (1996)... 

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