Pressure perturbation calorimetry of helical peptides

Barrett, Devin G.; Minder, C. Michael; Mian, Michelle U.; Whittington, Shelly J.; Cooper, W.; Fuchs, Kristin M; Tripathy, Ashutosh; Waters, Marcey L.; Creamer, T.; Pielak, Gary J.

doi:10.1002/prot.20819

Cited by 11 publications

(12 citation statements)

References 22 publications

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“…Large positive α 5 and large negative α 5–40 observed in apoA‐I and apoC‐I are probably dominated by hydration of charged residues that comprise about 1/3 of all groups in these proteins (Table I). High α‐helical content may also contribute to the large values of α 5 and α 5–40 , as suggested by a correlation between these values and the helical content reported in a PPC study of model peptides24: the peptides with the greatest α‐helix content showed most positive α 5 and most negative α 5–40 24. Furthermore, in globular proteins α 5–40 is roughly proportional to the solvent‐accessible surface area,21 which is relatively large in apolipoproteins.…”

Section: Resultsmentioning

confidence: 91%

“…In contrast, polar and charged “structure‐breaking” residues, which promote formation of less structured, more densely packed water, show α 5 > 0 and dα v ( T )/d T < 0 (Refs. 21–24 and references therein). Thus, in the temperature range from 5 to 40°C, where a typical protein is fully folded, α v ( T ) reflects combined effects of solvent‐accessible groups on protein hydration.…”

Section: Introductionmentioning

confidence: 99%

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Pressure perturbation calorimetry of apolipoproteins in solution and in model lipoproteins

Benjwal

Gursky

2009

Proteins

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High-density lipoproteins (HDL) are complexes of lipids and proteins (termed apolipoproteins) that remove cell cholesterol and protect from atherosclerosis. Apolipoproteins contain amphipathic α-helices that have high content (≥1/3) and distinct distribution of charged and apolar residues, adopt molten globule-like conformations in solution, and bind to lipid surfaces. We report the first pressure perturbation calorimetry (PPC) study of apolipoproteins. In solution, the main HDL protein, apoA-I, shows relatively large volume contraction, ΔV unf =-0.33%, and an apparent reduction in thermal expansivity upon unfolding, Δα unf ≤0, which has not been observed in other proteins. We propose that these values are dominated by increased charged residue hydration upon α-helical unfolding, which may result from disruption of multiple salt bridges. At 5°C, apoA-I shows large thermal expansion coefficient, α(5°) = 15·10 -4 K -1 , that rapidly declines upon heating from 5-40°C, α(40°)-α(5°)=-4·10 -4 K -1 ; apolipoprotein C-I shows similar values of α(5°) and α(40°). These values are larger than in globular proteins. They indicate dominant effect of charged residue hydration, which may modulate functional apolipoprotein interactions with a broad range of their protein and lipid ligands. The first PPC analysis of a protein-lipid complex is reported, which focuses on the chain melting transition in model HDL containing apoA-I or apoC-I, dimyristoyl phosphatidylcholine, and 0-20% cholesterol. The results may provide new insights into volumetric properties of HDL that modulate metabolic lipoprotein remodeling during cholesterol transport.

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Section: Resultsmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Pressure perturbation calorimetry of apolipoproteins in solution and in model lipoproteins

Benjwal

Gursky

2009

Proteins

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“…When pressure is applied to protein at different stages of fibrillation, the change in heat (ΔQ) reflects on their volumetric properties in terms of the relative change in volume (ΔV/V) and the thermal expansion coefficient (α). 56,[58][59][60][61][62][63]65,66…”

Section: Transmission Electron Microscopy a Jem 2100fmentioning

confidence: 99%

Physicochemical Insights into the Role of Drug Functionality in Fibrillation Inhibition of Bovine Serum Albumin

Ghosh

Kishore

2020

J. Phys. Chem. B

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To revert amyloid fibrils to their native state is a challenge in finding a solution to prevent neurodegenerative diseases. We have adopted a structure−property−energetics correlationbased approach with drugs (5-fluorouracil and hydroxyurea) having multiple hydrogen-bond donors and acceptors as inhibitors targeting different stages of bovine serum albumin fibrillation.We present here a quantitative comprehensive biophysical approach for identifying functionalities in molecules, which offers this feature in terms of polarity and hydrogen bonding. Our objective of identifying the functionality on a drug molecule that establishes effective intermolecular hydrogen bonding with β-strands of protein fibrils was achieved by combined calorimetric, spectroscopic, volumetric, and microscopic correlations. Relationships have been established among thermodynamic signatures, F 19 -NMR chemical shifts, hydrodynamic diameters, and thermal expansion coefficients to demonstrate that the open-chain molecule is a better inhibitor of fibrillation, but its efficiency decreases with the formation of amorphous aggregates, as compared to the molecule having a uracil ring. The results have provided quantitative insights into the role of polarity and hydrogen bonding in prevention of the fibrillation process. The approach adopted here highlights the physical chemistry underlying such biologically important processes and hence has significance in deriving guidelines for rational drug design.

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“…Pressure perturbation differential scanning calorimetry (PP‐DSC) is a new technique which permits determination of the thermal expansion coefficients of solute molecules in their dilute solution and thus estimates temperature‐induced changes of the partial volume of the solutes 1–4. A number of laboratories have used PP‐DSC for studying aqueous solutions of various low molecular weight compounds, lipids, and proteins 5–9. These studies led to an understanding that the thermal expansion coefficient carries information on hydration effects.…”

Section: Introductionmentioning

confidence: 99%

DNA hydration studied by pressure perturbation scanning microcalorimetry

2008

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Pressure perturbation differential scanning calorimetry was used to determine thermal expansion coefficients and thus temperature-induced volume changes of DNA duplexes differing in their GC/AT content. It was shown that the temperature-induced unfolding of the DNA duplexes proceeds with a significant increase of the thermal expansion coefficient and the partial volume of the DNA. Unusually, large temperature-induced changes in the partial volume were observed for an AT-rich dodecamer, a finding consistent with previous crystallographic studies showing the presence of highly ordered water molecules hydrating the minor groove of such duplexes. The data show that the density of this ordered water is substantially higher than that of the bulk water. This ordered water cannot, therefore, be equated to ice at normal pressures but it thermodynamically resembles ice formed at high pressures.

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Pressure perturbation calorimetry of helical peptides

Cited by 11 publications

References 22 publications

Pressure perturbation calorimetry of apolipoproteins in solution and in model lipoproteins

Pressure perturbation calorimetry of apolipoproteins in solution and in model lipoproteins

Physicochemical Insights into the Role of Drug Functionality in Fibrillation Inhibition of Bovine Serum Albumin

DNA hydration studied by pressure perturbation scanning microcalorimetry

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