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Protein Stabilization by Engineered Metal Chelation

Kellis, James T., Jr. and Todd, Robert J. and Arnold, Frances H. (1991) Protein Stabilization by Engineered Metal Chelation. Bio/Technology, 9 (10). pp. 994-995. ISSN 0733-222X. doi:10.1038/nbt1091-994.

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A ligand can shift a protein's folding/unfolding equilibrium by binding with higher affinity to the native state. A metal–chelating site consisting of two histidines separated by three residues (His–X_3–His) engineered into an α–helix provides a general and easily–implemented means for protein stabilization by this mechanism. We have tested this approach with the iso–1–cytochrome c of Saccharomyces cerevisiae substituted with histidine at positions 4 and 8 in its N–terminal α–helix. One mM Cu(II) complexed to iminodiacetate stabilizes the cytochrome c variant by ca. 1 kcal/mol, as determined by guanidinium chloride–induced unfolding. The protein's folding/unfolding equilibrium is shifted by a free energy equal to that calculated from the metal ion's preferential binding to the native protein. Given the ubiquity of surface α–helices and the additional possibility of inserting di–histidine chelating sites into turns and β–structures, we conclude that this is a useful method for protein stabilization.

Item Type:Article
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Arnold, Frances H.0000-0002-4027-364X
Additional Information:© 1991 Springer Nature Limited. Received 25 July 1991. Accepted 07 August 1991. Published 01 October 1991.
Issue or Number:10
Record Number:CaltechAUTHORS:20180822-140907669
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:89055
Deposited By: George Porter
Deposited On:22 Aug 2018 22:07
Last Modified:16 Nov 2021 00:31

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