Change in Heat Capacity for Enzyme Catalysis Determines Temperature Dependence of Enzyme Catalyzed Rates

Hobbs, Joanne K.; Jiao, Wanting; Easter, Ashley; Parker, E.J.; Schipper, Louis A.; Arcus, Vickery L.

doi:10.1021/acschembio.7b00065

Cited by 57 publications

(121 citation statements)

References 4 publications

(4 reference statements)

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“…35 For protein folding, DC p can be calculated fairly accurately based on changes in solvent accessible surface area. 22,23,34 Applying this approach, and assuming no structural change in the monomer upon dissociation, the estimated DC p,d for SOD1 is 0.5 kcal (mol dimer) 21 8C 21 , much lower than the experimental value. Notably, large DH d and DC p,d values have been reported for some other proteins, and were explained by significant protein conformational changes and/or changes in solvent binding upon subunit dissociation.…”

Section: Thermodynamics Reveal Apo Sod1 Dimer Dissociation Is Accompamentioning

confidence: 78%

Destabilization of the dimer interface is a common consequence of diverse ALS‐associated mutations in metal free SOD1

et al. 2015

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Neurotoxic misfolding of Cu, Zn-superoxide dismutase (SOD1) is implicated in causing amyotrophic lateral sclerosis, a devastating and incurable neurodegenerative disease. Diseaselinked mutations in SOD1 have been proposed to promote misfolding and aggregation by decreasing protein stability and increasing the proportion of less folded forms of the protein. Here we report direct measurement of the thermodynamic effects of chemically and structurally diverse mutations on the stability of the dimer interface for metal free (apo) SOD1 using isothermal titration calorimetry and size exclusion chromatography. Remarkably, all mutations studied, even ones distant from the dimer interface, decrease interface stability, and increase the population of monomeric SOD1. We interpret the thermodynamic data to mean that substantial structural perturbations accompany dimer dissociation, resulting in the formation of poorly packed and malleable dissociated monomers. These findings provide key information for understanding the mechanisms and energetics underlying normal maturation of SOD1, as well as toxic SOD1 misfolding pathways associated with disease. Furthermore, accurate prediction of protein-protein association remains very difficult, especially when large structural changes are involved in the process, and our findings provide a quantitative set of data for such cases, to improve modelling of protein association.

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Section: Thermodynamics Reveal Apo Sod1 Dimer Dissociation Is Accompamentioning

confidence: 78%

Destabilization of the dimer interface is a common consequence of diverse ALS‐associated mutations in metal free SOD1

et al. 2015

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“…The three parameters of their model (a, b, and c) have been shown to scale with thermodynamic parameters derived from MMRT (Liang et al, 2017). MMRT is an extension of the classical Transition State Theory (Eyring, 1935) and was developed to account for the temperature dependence of enzyme-catalyzed rates of reaction (Hobbs et al, 2013). The central feature of MMRT is the introduction of the parameter ΔC p ‡ , denoting the difference in heat capacity between the enzyme bound to the substrate for the reaction and the enzyme bound to the transition state for the reaction (for details, see Arcus et al, 2016 see Figure 1 for two examples, and Table 1 for a list of symbols).…”

Section: Gas Exchange Measurements and Treatment Of Temperature Resmentioning

confidence: 99%

Three physiological parameters capture variation in leaf respiration of Eucalyptus grandis, as elicited by short‐term changes in ambient temperature, and differing nitrogen supply

Kruse¹,

Rennenberg²,

Adams

2018

Plant Cell & Environment

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We used instantaneous temperature responses of CO -respiration to explore temperature acclimation dynamics for Eucalyptus grandis grown with differing nitrogen supply. A reduction in ambient temperature from 23 to 19 °C reduced light-saturated photosynthesis by 25% but increased respiratory capacity by 30%. Changes in respiratory capacity were not reversed after temperatures were subsequently increased to 27 °C. Temperature sensitivity of respiration measured at prevalent ambient temperature varied little between temperature treatments but was significantly reduced from ~105 kJ mol when supply of N was weak, to ~70 kJ mol when it was strong. Temperature sensitivity of respiration measured across a broader temperature range (20-40 °C) could be fully described by 2 exponent parameters of an Arrhenius-type model (i.e., activation energy of respiration at low reference temperature and a parameter describing the temperature dependence of activation energy). These 2 parameters were strongly correlated, statistically explaining 74% of observed variation. Residual variation was linked to treatment-induced changes in respiration at low reference temperature or respiratory capacity. Leaf contents of starch and soluble sugars suggest that respiratory capacity varies with source-sink imbalances in carbohydrate utilization, which in combination with shifts in carbon-flux mode, serve to maintain homeostasis of respiratory temperature sensitivity at prevalent growth temperature.

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“…These changes are not accompanied by a structurally different enzyme form, with the X-ray crystal structures of the WT and V200S enzymes being essentially invariant [16]. Molecular dynamics simulations suggest that the origin of the difference in DC z P is due to rigidification of the ground state relative to the transition state for V200S MalL when compared to the WT enzyme [16]. That is, the FEL for the enzyme-substrate complex is greatly constrained at the transition state implying significant changes to the distribution of vibrational modes along the reaction coordinate.…”

Section: Introductionmentioning

confidence: 99%

A complete thermodynamic analysis of enzyme turnover links the free energy landscape to enzyme catalysis

et al. 2017

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Our understanding of how enzymes work is coloured by static structure depictions where the enzyme scaffold is presented as either immobile, or in equilibrium between well-defined static conformations. Proteins, however, exhibit a large degree of motion over a broad range of timescales and magnitudes and this is defined thermodynamically by the enzyme free energy landscape (FEL). The role and importance of enzyme motion is extremely contentious. Much of the challenge is in the experimental detection of so called 'conformational sampling' involved in enzyme turnover. Herein we apply combined pressure and temperature kinetics studies to elucidate the full suite of thermodynamic parameters defining an enzyme FEL as it relates to enzyme turnover. We find that the key thermodynamic parameters governing vibrational modes related to enzyme turnover are the isobaric expansivity term and the change in heat capacity for enzyme catalysis. Variation in the enzyme FEL affects these terms. Our analysis is supported by a range of biophysical and computational approaches that specifically capture information on protein vibrational modes and the FEL (all atom flexibility calculations, red edge excitation shift spectroscopy and viscosity studies) that provide independent evidence for our findings. Our data suggest that restricting the enzyme FEL may be a powerful strategy when attempting to rationally engineer enzymes, particularly to alter thermal activity. Moreover, we demonstrate how rational predictions can be made with a rapid computational approach.

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Change in Heat Capacity for Enzyme Catalysis Determines Temperature Dependence of Enzyme Catalyzed Rates

Cited by 57 publications

References 4 publications

Destabilization of the dimer interface is a common consequence of diverse ALS‐associated mutations in metal free SOD1

Destabilization of the dimer interface is a common consequence of diverse ALS‐associated mutations in metal free SOD1

Three physiological parameters capture variation in leaf respiration of Eucalyptus grandis, as elicited by short‐term changes in ambient temperature, and differing nitrogen supply

A complete thermodynamic analysis of enzyme turnover links the free energy landscape to enzyme catalysis

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