Involvement of the chicken liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase sequence His444-Arg-Glu-Arg in modulation of the bisphosphatase activity by its kinase domain

Zhu, Ziyuan; LING, Song; Yang, Qi-En; Lin, Li

doi:10.1042/bj3570513

Cited by 4 publications

(6 citation statements)

References 19 publications

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“…This deletion also blunted the PKA-induced effects of phosphorylation on both activities. Truncation of the C-terminal 25-30 residues from the rat liver [132] and chicken liver [133] isoenzymes increased the k cat of FBPase-2 and abolished the effect of PKA-mediated phosphorylation to activate FBPase-2. A sequence His 444 -Arg-Glu-Arg 447 was identified in chicken liver PFK-2/FBPase-2, which mediates the repressive effect of the N-terminal PFK-2 domain on FBPase-2 activity [133].…”

Section: Rat Liver Pfk-2/fbpase-2mentioning

confidence: 99%

“…Truncation of the C-terminal 25-30 residues from the rat liver [132] and chicken liver [133] isoenzymes increased the k cat of FBPase-2 and abolished the effect of PKA-mediated phosphorylation to activate FBPase-2. A sequence His 444 -Arg-Glu-Arg 447 was identified in chicken liver PFK-2/FBPase-2, which mediates the repressive effect of the N-terminal PFK-2 domain on FBPase-2 activity [133]. It was proposed that phosphorylation by PKA could activate FBPase-2 by relieving the repression by the PFK-2 domain that is mediated by the two basic residues, His 444 and Arg 445 , in this sequence [133].…”

Section: Rat Liver Pfk-2/fbpase-2mentioning

confidence: 99%

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6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: head-to-head with a bifunctional enzyme that controls glycolysis

Rider

Bertrand

Vertommen

et al. 2004

Biochemical Journal

359

350

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Fru-2,6-P2 (fructose 2,6-bisphosphate) is a signal molecule that controls glycolysis. Since its discovery more than 20 years ago, inroads have been made towards the understanding of the structure-function relationships in PFK-2 (6-phosphofructo-2-kinase)/FBPase-2 (fructose-2,6-bisphosphatase), the homodimeric bifunctional enzyme that catalyses the synthesis and degradation of Fru-2,6-P2. The FBPase-2 domain of the enzyme subunit bears sequence, mechanistic and structural similarity to the histidine phosphatase family of enzymes. The PFK-2 domain was originally thought to resemble bacterial PFK-1 (6-phosphofructo-1-kinase), but this proved not to be correct. Molecular modelling of the PFK-2 domain revealed that, instead, it has the same fold as adenylate kinase. This was confirmed by X-ray crystallography. A PFK-2/FBPase-2 sequence in the genome of one prokaryote, the proteobacterium Desulfovibrio desulfuricans, could be the result of horizontal gene transfer from a eukaryote distantly related to all other organisms, possibly a protist. This, together with the presence of PFK-2/FBPase-2 genes in trypanosomatids (albeit with possibly only one of the domains active), indicates that fusion of genes initially coding for separate PFK-2 and FBPase-2 domains might have occurred early in evolution. In the enzyme homodimer, the PFK-2 domains come together in a head-to-head like fashion, whereas the FBPase-2 domains can function as monomers. There are four PFK-2/FBPase-2 isoenzymes in mammals, each coded by a different gene that expresses several isoforms of each isoenzyme. In these genes, regulatory sequences have been identified which account for their long-term control by hormones and tissue-specific transcription factors. One of these, HNF-6 (hepatocyte nuclear factor-6), was discovered in this way. As to short-term control, the liver isoenzyme is phosphorylated at the N-terminus, adjacent to the PFK-2 domain, by PKA (cAMP-dependent protein kinase), leading to PFK-2 inactivation and FBPase-2 activation. In contrast, the heart isoenzyme is phosphorylated at the C-terminus by several protein kinases in different signalling pathways, resulting in PFK-2 activation.

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Section: Rat Liver Pfk-2/fbpase-2mentioning

confidence: 99%

Section: Rat Liver Pfk-2/fbpase-2mentioning

confidence: 99%

6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: head-to-head with a bifunctional enzyme that controls glycolysis

Rider

Bertrand

Vertommen

et al. 2004

Biochemical Journal

359

350

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“…Phosphorylation of Ser-32 causes both a reduction of the kinase activity and an enhancement of the bisphosphatase activity resulting in a decrease in the kinase:bisphosphatase activity ratio and subsequently in increased hepatic glucose production, consistent with the fasting state [2]. Molecular rearrangements in the PFK-2/FBPase-2 dimer have been shown to be involved in the regulation of the enzyme activities of the kinase and the bisphosphatase [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Dimer interface rearrangement of the 6‐phosphofructo‐2‐kinase/fructose 2,6‐bisphosphatase rat liver isoenzyme by cAMP‐dependent Ser‐32 phosphorylation

et al. 2012

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Edited by Gianni CesareniKeywords: 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase Ser-32 phosphorylation Dimerization Bifunctional enzyme Mammalian two-hybrid system Fluorescence resonance energy transfer a b s t r a c tThe bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2) is a key regulator of carbohydrate metabolism in liver. The goal of this study was to elucidate the regulatory role of Ser-32 phosphorylation on the kinase domain mediated dimerization of PFK-2/ FBPase-2. Fluorescence-based mammalian two-hybrid and sensitized emission fluorescence resonance energy transfer analyses in cells revealed preferential binding within homodimers in contrast to heterodimers. Using isolated proteins a close proximity of two PFK-2/FBPase-2 monomers was only detectable in the phosphorylated enzyme dimer. Thus, a flexible kinase interaction mode exists, suggesting dimer conformation mediated coupling of hormonal and posttranslational enzyme regulation to the metabolic response in liver.

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“…To see this mechanism in action, one needs to clarify the position of the N-terminal tail relative to the interdomain hinge region in both the unphosphorylated and phosphorylated enzyme forms. In the absence of this information, no definitive conclusion can be drawn, since it cannot be ruled out that the mechanism of enzyme regulation by phosphorylation might involve some long-range conformational changes (38).…”

Section: Conclusion and Prospectsmentioning

confidence: 99%

“…A considerable step forward was made with the identification of the amino acid residues responsible for the effect exhibited by the C-terminal portion of the enzyme. Zhu et al have found that mutation of the sequence His 444 -Arg-Glu-Arg to Ala-Ala-Glu-Ala (numbering of the chicken liver enzyme) dramatically enhanced the catalytic rate of the bisphosphatase, abrogated the inhibition of the kinase domain, and removed the effect of PKA-catalyzed phosphorylation on activity, suggesting that amino acids within this tetrapeptide play a critical role in the repression of bisphosphatase activity by both the N-terminal kinase domain and the Cterminal tail itself (38). Okar et al (39) characterized the network of hydrogen bonds linking the amino acid residues which participate in catalysis, with the C-terminal His446 (numbering of the rat liver enzyme).…”

Section: -Phosphofructo-2-kinase/fructose-26-bisphosphatase Interdmentioning

confidence: 99%

Interdomain Communications in Bifunctional Enzymes: How Are Different Activities Coordinated?

Nagradova

2003

IUBMB Life

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SummaryAlthough bifunctional enzymes containing two different active centers located within separate domains are quite common in living systems, the significance of this bifunctionality is not always clear, and the molecular mechanisms of site-site interactions in such complex systems have come under the scrutiny of science only in recent years. This review summarizes recent data on the mechanisms of communication between active centers in bifunctional enzymes. Three types of enzymes are considered: (1) those catalyzing consecutive reactions of a metabolic pathway and exhibiting substrate channeling (glutamate synthase and imidazole glycerol phosphate synthase), (2) those catalyzing consecutive reactions without substrate channeling (lysine-ketoglutarate reductase/ saccharopine dehydrogenase), and (3) those catalyzing opposed reactions (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase). The functional role of interdomain communications is briefly discussed.IUBMB Life, 55: 459-466, 2003

show abstract

Involvement of the chicken liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase sequence His444-Arg-Glu-Arg in modulation of the bisphosphatase activity by its kinase domain

Cited by 4 publications

References 19 publications

6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: head-to-head with a bifunctional enzyme that controls glycolysis

6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: head-to-head with a bifunctional enzyme that controls glycolysis

Dimer interface rearrangement of the 6‐phosphofructo‐2‐kinase/fructose 2,6‐bisphosphatase rat liver isoenzyme by cAMP‐dependent Ser‐32 phosphorylation

Interdomain Communications in Bifunctional Enzymes: How Are Different Activities Coordinated?

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