Tang, Yi and Ghirlanda, Giovanna and Vaidehi, Nagarajan and Kua, Jeremy and Mainz, Daniel T. and Goddard, William A., III and DeGrado, William F. and Tirrell, David A. (2001) Stabilization of Coiled-Coil Peptide Domains by Introduction of Trifluoroleucine. Biochemistry, 40 (9). pp. 2790-2796. ISSN 0006-2960. doi:10.1021/bi0022588. https://resolver.caltech.edu/CaltechAUTHORS:20150122-091952579
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Abstract
Substitution of leucine residues by 5,5,5-trifluoroleucine at the d-positions of the leucine zipper peptide GCN4-p1d increases the thermal stability of the coiled-coil structure. The midpoint thermal unfolding temperature of the fluorinated peptide is elevated by 13 °C at 30 μM peptide concentration. The modified peptide is more resistant to chaotropic denaturants, and the free energy of folding of the fluorinated peptide is 0.5−1.2 kcal/mol larger than that of the hydrogenated form. A similarly fluorinated form of the DNA-binding peptide GCN4-bZip binds to target DNA sequences with affinity and specificity identical to those of the hydrogenated form, while demonstrating enhanced thermal stability. Molecular dynamics simulation on the fluorinated GCN4-p1d peptide using the Surface Generalized Born implicit solvation model revealed that the coiled-coil binding energy is 55% more favorable upon fluorination. These results suggest that fluorination of hydrophobic substructures in peptides and proteins may provide new means of increasing protein stability, enhancing protein assembly, and strengthening receptor−ligand interactions.
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Additional Information: | Copyright © 2001 American Chemical Society. Published In Issue March 06, 2001. Publication Date (Web): February 7, 2001. Received September 26, 2000. Revised Manuscript Received December 22, 2000. We thank Dr. James D. Lear for writing the Igor Pro procedures.. This work was supported by a grant from the U.S. Army Research Office to D.A.T. and by NIH Grant GM54616 to W.F.D. Y. Tang is grateful for a graduate research fellowship from the Whitaker Foundation. | |||||||||
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Issue or Number: | 9 | |||||||||
DOI: | 10.1021/bi0022588 | |||||||||
Record Number: | CaltechAUTHORS:20150122-091952579 | |||||||||
Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20150122-091952579 | |||||||||
Official Citation: | Stabilization of Coiled-Coil Peptide Domains by Introduction of Trifluoroleucine Yi Tang, Giovanna Ghirlanda, Nagarajan Vaidehi, Jeremy Kua, Daniel T. Mainz, William A. Goddard III, William F. DeGrado, and David A. Tirrell. Biochemistry 2001 40 (9), 2790-2796 | |||||||||
Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | |||||||||
ID Code: | 53982 | |||||||||
Collection: | CaltechAUTHORS | |||||||||
Deposited By: | Katherine Johnson | |||||||||
Deposited On: | 22 Jan 2015 17:26 | |||||||||
Last Modified: | 10 Nov 2021 20:25 |
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