The Crystal Structures of Eukaryotic Phosphofructokinases from Baker's Yeast and Rabbit Skeletal Muscle

Banaszak, K.; Mechin, I.; Obmolova, Galina; Oldham, Michael L.; Chang, Sheng-Fuh; Ruíz, Teresa; Radermacher, Michael; Kopperschläger, Gèrhard; Rypniewski, W.

doi:10.1016/j.jmb.2011.01.019

Cited by 46 publications

(61 citation statements)

References 50 publications

(55 reference statements)

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“…were selected based on the crystal structure of rabbit skeletal muscle Pfk (Protein Data Bank (PDB): IDs 3O8N and 3O8L). These residues participate in the proposed ADP activator and the ATP inhibitor binding sites (13,15) and are conserved between the human and rabbit muscle Pfk.…”

Section: Methodsmentioning

confidence: 99%

“…For example, citrate inhibits the enzyme through interaction with sites that have evolved from a duplicated allosteric site (phosphoenolpyruvate binding site) (11,12), whereas sites for activators, e.g. fructose 2,6-bisphosphate, have evolved from the catalytic site (Fru-6-P) of the ancestral precursor (7,13). In contrast, the ATP substrate binding site from the ancestral prokaryotic Pfk did not evolve to a new inhibitory ATP binding pocket (13,15), and it remains unclear as to how adenine nucleotides implement their allosteric inhibitory (ATP) and activating (AMP) effects.…”

mentioning

confidence: 99%

“…fructose 2,6-bisphosphate, have evolved from the catalytic site (Fru-6-P) of the ancestral precursor (7,13). In contrast, the ATP substrate binding site from the ancestral prokaryotic Pfk did not evolve to a new inhibitory ATP binding pocket (13,15), and it remains unclear as to how adenine nucleotides implement their allosteric inhibitory (ATP) and activating (AMP) effects. Note that ATP serves as a substrate and as an allosteric inhibitor of eukaryotic Pfk.…”

mentioning

confidence: 99%

“…In 2011, crystal structures of three eukaryotic Pfk from the yeasts Pichia pastoris (15) and Saccharomyces cerevisiae (13) and from rabbit muscle (13) were determined. In the crystal structure of P. pastoris Pfk, an additional ATP binding pocket was found in each ␤ chain, which was presumed to be an inactivating site (15).…”

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confidence: 99%

“…In the structure of rabbit muscle Pfk, this ATP binding site was also discovered in the N-terminal domain of each subunit with either ADP or ATP bound to it. An additional novel ADP binding site was found in the center of each subunit (13). This was proposed as an activating (ADP binding) site because replacement by ATP failed (see Fig.…”

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confidence: 99%

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Functional Linkage of Adenine Nucleotide Binding Sites in Mammalian Muscle 6-Phosphofructokinase

Brüser¹,

Kirchberger²,

Kloos

et al. 2012

Journal of Biological Chemistry

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Background: Crystal structures of 6-phosphofructokinases revealed nucleotide binding sites with unknown functional relevance. Results: Function of two allosteric nucleotide binding sites was determined by mutagenesis and kinetic studies and revealed reciprocal linkage of both. Conclusion: Activity of mammalian Pfk is regulated by structurally linked new allosteric sites. Significance: Reciprocal linkage between allosteric binding sites evolved convergent in prokaryotes and eukaryotes.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

mentioning

confidence: 99%

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Functional Linkage of Adenine Nucleotide Binding Sites in Mammalian Muscle 6-Phosphofructokinase

Brüser¹,

Kirchberger²,

Kloos

et al. 2012

Journal of Biological Chemistry

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A Designed Enzyme Promotes Selective Post‐translational Acylation

et al. 2018

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A computationally designed, allosterically regulated catalyst (CaM M144H) produced by substituting a single residue in calmodulin, a non-enzymatic protein, is capable of efficient and site selective post-translational acylation of lysines in peptides with highly diverse sequences. Calmodulin's binding partners are involved in regulating a large number of cellular processes; this new chemical-biology tool will help to identify them and provide structural insight into their interactions with calmodulin.

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Phosphofructokinase type 1 kinetics, isoform expression, and gene polymorphisms in cancer cells

Moreno‐Sánchez

Marín‐Hernández

Gallardo‐Pérez

et al. 2012

J of Cellular Biochemistry

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Kinetic analysis of PFK-1 from rodent AS-30D, and human HeLa and MCF-7 carcinomas revealed sigmoidal [fructose 6-phosphate, Fru6P]-rate curves with different V(m) values when varying the allosteric activator fructose 2,6 bisphosphate (Fru2,6BP), AMP, Pi, NH(4)(+), or K(+). The rate equation that accurately predicted this behavior was the exclusive ligand binding concerted transition model together with non-essential hyperbolic activation. PFK-1 from rat liver and heart also exhibited the mixed cooperative-hyperbolic kinetic behavior regarding activators. Lowering pH induced decreased affinity for Fru6P, Fru2,6BP, citrate, and ATP (as inhibitor); as well as decreased V(m) and increased content of inactive (T) enzyme forms. High K(+) prompted increased (Fru6P) or decreased (activators) affinities; increased V(m); and increased content of active (R) enzyme forms. mRNA expression analysis and nucleotide sequencing showed that the three PFK-1 isoforms L, M, and C are transcribed in the three carcinomas. However, proteomic analysis indicated the predominant expression of L in liver, of M in heart and MCF-7 cells, of L>M in AS-30D cells, and of C in HeLa cells. PFK-1M showed the highest affinities for F6P and citrate and the lowest for ATP (substrate) and F2,6BP; PFK-1L showed the lowest affinity for F6P and the highest for F2,6BP; and PFK-1C exhibited the highest affinity for ATP (substrate) and the lowest for citrate. Thus, the present work documents the kinetic signature of each PFK-1 isoform, and facilitates the understanding of why this enzyme exerts significant or negligible glycolysis flux-control in normal or cancer cells, respectively, and how it regulates the onset of the Pasteur effect.

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The Crystal Structures of Eukaryotic Phosphofructokinases from Baker's Yeast and Rabbit Skeletal Muscle

Cited by 46 publications

References 50 publications

Functional Linkage of Adenine Nucleotide Binding Sites in Mammalian Muscle 6-Phosphofructokinase

Functional Linkage of Adenine Nucleotide Binding Sites in Mammalian Muscle 6-Phosphofructokinase

A Designed Enzyme Promotes Selective Post‐translational Acylation

Phosphofructokinase type 1 kinetics, isoform expression, and gene polymorphisms in cancer cells

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