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Increasing Protein Conformational Stability by Optimizing β-Turn Sequence
Journal article   Open access   Peer reviewed

Increasing Protein Conformational Stability by Optimizing β-Turn Sequence

Saul R. Trevino, Stephanie Schaefer, J. Martin Scholtz and C. Nick Pace
Journal of molecular biology, Vol.373(1), pp.211-218
2007
DOI: 10.1016/j.jmb.2007.07.061
PMCID: PMC2084202
PMID: 17765922
url
https://www.ncbi.nlm.nih.gov/pmc/articles/2084202View
Open Access

Abstract

Protein conformational stability is an important concern in many fields. Here, we describe a strategy for significantly increasing conformational stability by optimizing β-turn sequence. Proline and glycine residues are statistically preferred at several β-turn positions, presumably because their unique side-chains contribute favorably to conformational stability in certain β-turn positions. However, β-turn sequences often deviate from preferred proline or preferred glycine. Therefore, our strategy involves replacing non-proline and non-glycine β-turn residues with preferred proline or preferred glycine residues. Here, we develop guidelines for selecting appropriate mutations, and present results for five mutations (S31P, S42G, S48P, T76P, and Q77G) that significantly increase the conformational stability of RNase Sa. The increases in stability ranged from 0.7 kcal/mol to 1.3 kcal/mol. The strategy was successful in overlapping or isolated β-turns, at buried (up to 50%) or completely exposed sites, and at relatively flexible or inflexible sites. Considering the significant number of β-turn residues in every globular protein and the frequent deviation of β-turn sequences from preferred proline and preferred glycine residues, this simple, efficient strategy will be useful for increasing the conformational stability of proteins.
 glycine proline protein conformational stability β-turn

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