To boil an egg: substrate binding affects critical stability in thermal unfolding of proteins
Thermal unfolding of proteins is used extensively in screening of drug candidates because molecular interactions with ligands and substrates affect strongly protein stability, transition temperature, and cooperativity. We use synchrotron radiation circular dichroism to monitor the thermal evolution...
| Main Authors: | , , , , , |
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| Format: | Article |
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American Chemical Society
2018
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| Online Access: | https://eprints.nottingham.ac.uk/50690/ |
| _version_ | 1848798315443912704 |
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| author | Hussain, Rohanah Hughes, Charlotte S. Jávorfi, Tamás Siligardi, Giuliano Williams, Paul Bonev, Boyan B. |
| author_facet | Hussain, Rohanah Hughes, Charlotte S. Jávorfi, Tamás Siligardi, Giuliano Williams, Paul Bonev, Boyan B. |
| author_sort | Hussain, Rohanah |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Thermal unfolding of proteins is used extensively in screening of drug candidates because molecular interactions with ligands and substrates affect strongly protein stability, transition temperature, and cooperativity. We use synchrotron radiation circular dichroism to monitor the thermal evolution of secondary structure in proteins as they approach the melting point and the impact of substrate on their thermal behavior. Using Landau free energy expansion, we quantify transition strength and proximity to a critical point through the relative separation τ+ between the transition temperature Tm and the spinodal T+, obtained from the equation of state. The weakest transition was observed in lysozyme with τ+ = −0.0167 followed by holo albumin with τ+ = −0.0208 with the strongest transition in monomeric apo albumin τ+ = − 0.0242. A structural transition at 45 °C in apo albumin leads to a noncooperative melt with τ+ = −0.00532 and amyloidogenic increase in beta content. |
| first_indexed | 2025-11-14T20:17:49Z |
| format | Article |
| id | nottingham-50690 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:17:49Z |
| publishDate | 2018 |
| publisher | American Chemical Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-506902020-05-04T19:30:56Z https://eprints.nottingham.ac.uk/50690/ To boil an egg: substrate binding affects critical stability in thermal unfolding of proteins Hussain, Rohanah Hughes, Charlotte S. Jávorfi, Tamás Siligardi, Giuliano Williams, Paul Bonev, Boyan B. Thermal unfolding of proteins is used extensively in screening of drug candidates because molecular interactions with ligands and substrates affect strongly protein stability, transition temperature, and cooperativity. We use synchrotron radiation circular dichroism to monitor the thermal evolution of secondary structure in proteins as they approach the melting point and the impact of substrate on their thermal behavior. Using Landau free energy expansion, we quantify transition strength and proximity to a critical point through the relative separation τ+ between the transition temperature Tm and the spinodal T+, obtained from the equation of state. The weakest transition was observed in lysozyme with τ+ = −0.0167 followed by holo albumin with τ+ = −0.0208 with the strongest transition in monomeric apo albumin τ+ = − 0.0242. A structural transition at 45 °C in apo albumin leads to a noncooperative melt with τ+ = −0.00532 and amyloidogenic increase in beta content. American Chemical Society 2018-02-05 Article PeerReviewed Hussain, Rohanah, Hughes, Charlotte S., Jávorfi, Tamás, Siligardi, Giuliano, Williams, Paul and Bonev, Boyan B. (2018) To boil an egg: substrate binding affects critical stability in thermal unfolding of proteins. Journal of Physical Chemistry B, 122 (8). pp. 2213-2218. ISSN 1520-52707 https://pubs.acs.org/doi/10.1021/acs.jpcb.7b10643 doi:10.1021/acs.jpcb.7b10643 doi:10.1021/acs.jpcb.7b10643 |
| spellingShingle | Hussain, Rohanah Hughes, Charlotte S. Jávorfi, Tamás Siligardi, Giuliano Williams, Paul Bonev, Boyan B. To boil an egg: substrate binding affects critical stability in thermal unfolding of proteins |
| title | To boil an egg: substrate binding affects critical stability in thermal unfolding of proteins |
| title_full | To boil an egg: substrate binding affects critical stability in thermal unfolding of proteins |
| title_fullStr | To boil an egg: substrate binding affects critical stability in thermal unfolding of proteins |
| title_full_unstemmed | To boil an egg: substrate binding affects critical stability in thermal unfolding of proteins |
| title_short | To boil an egg: substrate binding affects critical stability in thermal unfolding of proteins |
| title_sort | to boil an egg: substrate binding affects critical stability in thermal unfolding of proteins |
| url | https://eprints.nottingham.ac.uk/50690/ https://eprints.nottingham.ac.uk/50690/ https://eprints.nottingham.ac.uk/50690/ |