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Controlling peptide folding with repulsive interactions between phosphorylated amino acids and tryptophan.

ABSTRACT: Phosphorylated amino acids were incorporated into a designed beta-hairpin peptide to study the effect on beta-hairpin structure when the phosphate group is positioned to interact with a tryptophan residue on the neighboring strand. The three commonly phosphorylated residues in biological systems, serine, threonine, and tyrosine, were studied in the same beta-hairpin system. It was found that phosphorylation destabilizes the hairpin structure by approximately 1.0 kcal/mol, regardless of the type of phosphorylated residue. In contrast, destabilization due to glutamic acid was about 0.3 kcal/mol. Double mutant cycles and pH studies are consistent with a repulsive interaction as the source of destabilization. These findings demonstrate a novel mechanism by which phosphorylation may influence protein structure and function.

SUBMITTER: Riemen AJ

PROVIDER: S-EPMC2757742 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Controlling peptide folding with repulsive interactions between phosphorylated amino acids and tryptophan.

Riemen Alexander J AJ Waters Marcey L ML

Journal of the American Chemical Society 20091001 39

Phosphorylated amino acids were incorporated into a designed beta-hairpin peptide to study the effect on beta-hairpin structure when the phosphate group is positioned to interact with a tryptophan residue on the neighboring strand. The three commonly phosphorylated residues in biological systems, serine, threonine, and tyrosine, were studied in the same beta-hairpin system. It was found that phosphorylation destabilizes the hairpin structure by approximately 1.0 kcal/mol, regardless of the type ...[more]

PMID: 19743848

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