[17] Chemical synthesis of fructose 2,6-bisphosphate

Pilkis, S J; el-Maghrabi, M R; Cumming, Dale A.; Pilkis, J; Claus, Thomas H.

doi:10.1016/s0076-6879(82)89019-8

Cited by 74 publications

(107 citation statements)

References 11 publications

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“…Another variant of the pentose phosphate pathway in liver is shown in fig.3 in which phosphofructokinase and fructose bisphosphatase play a r61e in the interconversion of altro heptulose 7-P and altro heptulose 1,7-P2. Since there are no convincing control mechanisms demonstrated for controlling flux of carbon through the non-oxidative pentose pathway [37], the operation of the pathway shown in fig.3 would serve to regulate the interconversion of hexose and pentose phosphates since phosphofructokinase and fructose bisphosphatase are under hormonal control [1][2][3][4][5][6][7]. The labelling experiments performed in hepatocytes [36] are consistent with, but do not prove, the operation of the scheme in fig.3.…”

Section: Resultsmentioning

confidence: 99%

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Regulation of hepatic altro heptulose 1,7‐bisphosphate levels and control of flux through the pentose pathway by fructose 2,6‐bisphosphate

Blackmore

Shuman

1982

FEBS Letters

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Section: Resultsmentioning

confidence: 99%

“…The regulation of carbon flux through the hepatic fructose bisphosphatase-phosphofructokinase substrate cycle is regulated, in part, by the level of a novel sugar phosphate fructose 2,6-P2 [1][2][3][4][5][6][7]. Methods for its synthesis and its anomeric specificity have been reported [8,9].…”

Section: Introductionmentioning

confidence: 99%

Regulation of hepatic altro heptulose 1,7‐bisphosphate levels and control of flux through the pentose pathway by fructose 2,6‐bisphosphate

Blackmore

Shuman

1982

FEBS Letters

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“…Inhibition by AMP is cooperative, with a Hill coefficient near 2 (Taketa & Pogell, 1965;Nimmo & Tipton, 1975a), whereas Fru-2,6-P2 binds to the active sites of the enzyme (Ke et al, 1989a) in competition with the substrate Fru-1,6-P2 (Pilkis et al, 1981). The AMP binding site on each subunit is 28 A distant from the active site (Keet al, 1991a) and the metal-binding sites are located between the Fru-1,6-P, and AMP domains (Ke et al, 1990).…”

mentioning

confidence: 99%

Crystal structures of the active site mutant (Arg‐243 → Ala) in the T and R allosteric states of pig kidney fructose‐1,6‐bisphosphatase expressed in escherichia coli

et al. 1996

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The active site of pig kidney fructose-l,6-bisphosphatase (EC 3.1.3.11) is shared between subunits, Arg-243 of one chain interacting with fructose-l,6-bisphosphate or fructose-2,6-bisphosphate in the active site of an adjacent chain. In this study, we present the X-ray structures of the mutant version of the enzyme with Arg-243 replaced by alanine, crystallized in both T and R allosteric states. Kinetic characteristics of the altered enzyme showed the magnesium binding and inhibition by AMP differed slightly; affinity for the substrate fructose-l,6-bisphosphate was reduced IO-fold and affinity for the inhibitor fructose-2,6-bisphosphate was reduced 1,000-fold (Giroux E, Williams MK, Kantrowitz ER, 1994, J Biol Chern 269:31404-31409). The X-ray structures show no major changes in the organization of the active site compared with wild-type enzyme, and the structures confirm predictions of molecular dynamics simulations involving Lys-269 and Lys-274. Comparison of two independent models of the T form structures have revealed small but significant changes in the conformation of the bound AMP molecules and small reorganization of the active site correlated with the presence of the inhibitor. The differences in kinetic properties of the mutant enzyme indicate the key importance of Arg-243 in the function of fructose-1,6-bisphosphatase. Calculations using the X-ray structures of the Arg-243 + Ala enzyme suggest that the role of Arg-243 in the wild-type enzyme is predominantly electrostatic in nature.

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“…This enzyme is strongly inhibited by fructose 2,6-P2, which enhances the allosteric inhibition produced by AMP [1,21, and is also inhibited by excess substrate [3]. The mechanism of inhibition of fructose-l,6-bisphosphatase by fructose 2,6-P2 is still a matter of controversy, with some reports in favor of a purely competitive process through interaction with the catalytic site [2,[4][5][6][7][8][9], while experiments from other laboratories point to an allosteric inhibition, suggesting a separate binding site for fructose 2,6-P2 [1,[10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Allosteric inhibition of Dictyostelium discoideum fructose‐1,6‐bisphosphatase by fructose 2,6‐bisphosphate

et al. 1988

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it has been found that the inhibition Of Dictyostelium discoideum fructose-l,6-bisphosphatase by fructose 2,6-P 2 greatly diminished when the pH was raised to the range 8.5 -9.5, which resulted in a marked decrease of the affinity for the inhibitor with no change in the Km for the substrate. This provides evidence for the involvement of an allosteric site for fructose 2,6-P 2. Moreover, the fact that excess substrate inhibition also decreased at the pH values for minimal fructose 2,6-P 2 inhibition, and was essentially abolished in the presence of fructose 2,6-P2, strongly suggests that this inhibition takes place by binding of fructose 1,6-P 2 as a weak analogue of the physiological effector fructose 2,6-P 2.Fructose-1,6-bisphosphatase; Fructose 2,6-bisphosphate; (Dictyostelium discoideum)

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[17] Chemical synthesis of fructose 2,6-bisphosphate

Cited by 74 publications

References 11 publications

Regulation of hepatic altro heptulose 1,7‐bisphosphate levels and control of flux through the pentose pathway by fructose 2,6‐bisphosphate

Regulation of hepatic altro heptulose 1,7‐bisphosphate levels and control of flux through the pentose pathway by fructose 2,6‐bisphosphate

Crystal structures of the active site mutant (Arg‐243 → Ala) in the T and R allosteric states of pig kidney fructose‐1,6‐bisphosphatase expressed in escherichia coli

Allosteric inhibition of Dictyostelium discoideum fructose‐1,6‐bisphosphatase by fructose 2,6‐bisphosphate

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