PROBING PROTEIN STABILITY WITH UNNATURAL AMINO-ACIDS

被引:139
作者
MENDEL, D
ELLMAN, JA
CHANG, ZY
VEENSTRA, DL
KOLLMAN, PA
SCHULTZ, PG
机构
[1] UNIV CALIF BERKELEY, DEPT CHEM, BERKELEY, CA 94720 USA
[2] LAWRENCE BERKELEY LAB, CTR ADV MAT, BERKELEY, CA 94720 USA
[3] UNIV CALIF SAN FRANCISCO, DEPT PHARMACEUT CHEM, SAN FRANCISCO, CA 94143 USA
关键词
D O I
10.1126/science.1615324
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 (i) leucine (wt), norvaline, ethyl-glycine, and alanine to measure the cost of stepwise removal of methyl groups from the hydrophobic core, (ii) norvaline and O-methyl serine to evaluate the effects of side chain solvation, and (iii) 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.
引用
收藏
页码:1798 / 1802
页数:5
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