Probing protein stability with unnatural amino acids

Journal Article · Fri Jun 26 00:00:00 EDT 1992 · Science (Washington, D.C.); (United States)

DOI:https://doi.org/10.1126/science.1615324· OSTI ID:7014231

Mendel, D; Ellman, J A; Chang, Zhiyuh; Veenstra, D L; Kollman, P A; Schultz, P G ^[1]

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1. Lawrence Berkeley Lab., CA (United States)

Unnatural amino acid mutagenesis, in combination with molecular modeling and simulation techniques, was used to probe the effect of side chain structure on protein stability. Specific replacements at position 133 in T4 lysozyme included (1) leucine (wt), norvaline, ethylglycine, and alanine to measure the cost of stepwise removal of methyl groups from the hydrophobic core, (2) norvaline and O-methyl serine to evaluate the effects of side chain solvation, and (3) leucine, S,S-2-amino-4-methylhexanoic acid, and S-2-amino-3-cyclopentylpropanoic acid to measure the influence of packing density and side chain conformational entropy on protein stability. All of these factors (hydrophobicity, packing, conformational entropy, and cavity formation) significantly influence protein stability and must be considered when analyzing any structural change to proteins.

• DOE Contract Number: AC03-76SF00098
• OSTI ID: 7014231
• Journal Information: Science (Washington, D.C.); (United States), Journal Name: Science (Washington, D.C.); (United States) Vol. 256:5065; ISSN SCIEA; ISSN 0036-8075
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
ALANINES
AMINO ACIDS
CARBOXYLIC ACIDS
ENZYMES
GLYCINE
GLYCOSYL HYDROLASES
HYDROLASES
HYDROXY ACIDS
LEUCINE
LYSOZYME
MATHEMATICAL MODELS
MUTAGENESIS
O-GLYCOSYL HYDROLASES
ORGANIC ACIDS
ORGANIC COMPOUNDS
PROTEIN STRUCTURE
PROTEINS
SERINE
SIMULATION
STABILITY
VALINE