Studying the phosphoryl transfer mechanism of the<i>E. coli</i>phosphofructokinase-2: from X-ray structure to quantum mechanics/molecular mechanics simulations

Murillo-López, Juliana A.; Zinovjev, Kirill; Pereira, H.M.; Caniuguir, A.; Garratt, R.C.; Babul, Jorge; Recabarren, Rodrigo; Alzate‐Morales, Jans; Caballero, Julio; Tuñón, Iñaki; Cabrera, Ricardo

doi:10.1039/c9sc00094a

Cited by 19 publications

(25 citation statements)

References 60 publications

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“…This approach has been successfully applied to different enzymatic reactions. 50,75,[79][80][81][82][83][84] Figure 3 shows the choice of the CVs for string method and path CV calculations. CVs 1 and 2 describe the breaking and formation of P-O bonds, respectively, while CVs and 4 represent the proton transfer from the threonine's hydroxyl group to Asp127.…”

Section: Qm/mm Free Energy Calculationsmentioning

confidence: 99%

How a Second Mg²⁺ Ion Affects the Phosphoryl-Transfer Mechanism in a Protein Kinase: A Computational Study

et al. 2020

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Mg 2+ ions are essential for the proper functioning of protein kinases and their roles in kinase activity have been studied for years. However, recent investigations have shed new light into how these metal cofactors modulate the catalytic activity, and new functions for them have been assigned. As an example, it has been found that in CDK2 (cyclin-dependent kinase 2), an enzyme that had been postulated to work

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Section: Qm/mm Free Energy Calculationsmentioning

confidence: 99%

How a Second Mg²⁺ Ion Affects the Phosphoryl-Transfer Mechanism in a Protein Kinase: A Computational Study

et al. 2020

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“…Our results suggest smaller channel spacings the continuous changing of energy barriers due to the continuous variation of water configurational excess entropy with temperature. It appears that the Arrhenius to super-Arrhenius behavior could be a more generic feature arising from the interplay of water confinement motions and temperature effects rather than the details of the chemical reaction steps 15 . Note also that such a scenario agrees with the findings of Ref.…”

Section: Discussionmentioning

confidence: 99%

“…Because the PFK-1 A subunit has more similar reaction conformations than the B subunit, molecular dynamics simulations were performed on a globular protein constructed of a PFK-1 (PDB entry 1PFK) A subunit, referred to as a many species structure 1 , 15 , 45 , 55 , 56 , in of dilute aqueous solution. MD simulations were performed with the AMBER 14 package 57 using a 0.1 ps integration time step and periodic boundary conditions with the 124 × 115 × 131 Å 3 box.…”

Section: Methodsmentioning

confidence: 99%

“…By assuming that the activation energy varies with temperature E a (T), we were able to obtain its physical meaning, that the super-Arrhenius behavior would be related to the diffusion kinetics term 9,13 . Therefore, it is worthwhile to investigate how this diffusion kinetics term works at the molecular level [14][15][16] . There has been an increasing number of studies measuring the temperature dependence of enzyme reactions, showing super-Arrhenius behaviors 12,[17][18][19][20][21][22][23] .…”

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confidence: 99%

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Temperature effect on water dynamics in tetramer phosphofructokinase matrix and the super-arrhenius respiration rate

Yang

et al. 2021

Sci Rep

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Advances in understanding the temperature effect on water dynamics in cellular respiration are important for the modeling of integrated energy processes and metabolic rates. For more than half a century, experimental studies have contributed to the understanding of the catalytic role of water in respiration combustion, yet the detailed water dynamics remains elusive. We combine a super-Arrhenius model that links the temperature-dependent exponential growth rate of a population of plant cells to respiration, and an experiment on isotope labeled 18O2 uptake to H218O transport role and to a rate-limiting step of cellular respiration. We use Phosphofructokinase (PFK-1) as a prototype because this enzyme is known to be a pacemaker (a rate-limiting enzyme) in the glycolysis process of respiration. The characterization shows that PFK-1 water matrix dynamics are crucial for examining how respiration (PFK-1 tetramer complex breathing) rates respond to temperature change through a water and nano-channel network created by the enzyme folding surfaces, at both short and long (evolutionary) timescales. We not only reveal the nano-channel water network of PFK-1 tetramer hydration topography but also clarify how temperature drives the underlying respiration rates by mapping the channels of water diffusion with distinct dynamics in space and time. The results show that the PFK-1 assembly tetramer possesses a sustainable capacity in the regulation of the water network toward metabolic rates. The implications and limitations of the reciprocal-activation–reciprocal-temperature relationship for interpreting PFK-1 tetramer mechanisms are briefly discussed.

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“…This may avoid premature hydrolysis of the γ-phosphate of ATP, as reported in ribokinases. 23,[25][26] Given the close functional relationship between of SF kinase (YihV) and PfkB and TPK, sequence-and structure-based analysis of their binding sites was undertaken. Two conserved motifs have been described in these phosphosugar kinases, the TR and GXGDXX motifs, responsible for substrate binding and catalysis, respectively.…”

Section: Sf Kinase Is Allosterically Regulated By Central Metabolitesmentioning

confidence: 99%

The Molecular Basis of Sulfosugar Selectivity in Sulfoglycolysis

Sharma¹,

Abayakoon²,

Epa³

et al. 2021

Preprint

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The sulfosugar sulfoquinovose (SQ) is produced by essentially all photosynthetic organisms on earth and is metabolized bacteria through the process of sulfoglycolysis. The sulfoglycolytic Embden-Meyerhof-Parnas pathway metabolises SQ to produce dihydroxyacetone phosphate and sulfolactaldehyde and is analogous to the classical Embden-Meyerhof-Parnas glycolysis pathway for the metabolism of glucose-6-phosphate, though the former only provides one C3 fragment to central metabolism, with excretion of the other C3 fragment as dihydroxypropanesulfonate. Here, we report a comprehensive structural and biochemical analysis of the three core steps of sulfoglycolysis catalyzed by SQ isomerase, sulfofructose (SF) kinase and sulfofructose-1-phosphate aldolase. Our data shows that despite the superficial similarity of this pathway to glycolysis, the sulfoglycolytic enzymes are specific for SQ metabolites and are not catalytically active on related metabolites from glycolytic pathways. This observation is rationalized by 3D structures of each of these enzymes, which reveal the presence of conserved sulfonate-binding pockets. We show that SQ isomerase acts preferentially on the b-anomer of SQ and reversibly produces both SF and sulforhamnose (SR), a previously unknown sugar that acts as a transcriptional regulator for the transcriptional repressor CsqR that regulates SQ-utilisation. We also demonstrate that SF kinase is a key regulatory enzyme for the pathway that experiences complex allosteric modulation by the metabolites AMP, ADP, ATP, F6P, FBP, PEP, and citrate. This body of work provides fresh insights into the mechanism, specificity and regulation of sulfoglycolysis and has important implications for understanding how this biochemistry interfaces with central metabolism in prokaryotes to process this major repository of biogeochemical sulfur.

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Studying the phosphoryl transfer mechanism of theE. coliphosphofructokinase-2: from X-ray structure to quantum mechanics/molecular mechanics simulations

Abstract: Phosphofructokinases catalyze the ATP-dependent phosphorylation of fructose-6-phosphate and they are highly regulated.

Cited by 19 publications

References 60 publications

How a Second Mg²⁺ Ion Affects the Phosphoryl-Transfer Mechanism in a Protein Kinase: A Computational Study

How a Second Mg²⁺ Ion Affects the Phosphoryl-Transfer Mechanism in a Protein Kinase: A Computational Study

Temperature effect on water dynamics in tetramer phosphofructokinase matrix and the super-arrhenius respiration rate

The Molecular Basis of Sulfosugar Selectivity in Sulfoglycolysis

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Studying the phosphoryl transfer mechanism of theE. coliphosphofructokinase-2: from X-ray structure to quantum mechanics/molecular mechanics simulations

Abstract: Phosphofructokinases catalyze the ATP-dependent phosphorylation of fructose-6-phosphate and they are highly regulated.

Cited by 19 publications

References 60 publications

How a Second Mg2+ Ion Affects the Phosphoryl-Transfer Mechanism in a Protein Kinase: A Computational Study

How a Second Mg2+ Ion Affects the Phosphoryl-Transfer Mechanism in a Protein Kinase: A Computational Study

Temperature effect on water dynamics in tetramer phosphofructokinase matrix and the super-arrhenius respiration rate

The Molecular Basis of Sulfosugar Selectivity in Sulfoglycolysis

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Product

Resources

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How a Second Mg²⁺ Ion Affects the Phosphoryl-Transfer Mechanism in a Protein Kinase: A Computational Study

How a Second Mg²⁺ Ion Affects the Phosphoryl-Transfer Mechanism in a Protein Kinase: A Computational Study