Stabilizing and destabilizing effects of phenylalanine --> F5-phenylalanine mutations on the folding of a small protein.
We report a systematic evaluation of phenylalanine-to-pentafluorophenylalanine (Phe --> F5-Phe) mutants for the 35-residue chicken villin headpiece subdomain (c-VHP), the hydrophobic core of which features a cluster of three Phe side chains (residues 6, 10, and 17). Phe --> F5-Phe mutations are interesting because aryl-perfluoroaryl interactions of optimal geometry are intrinsically more favorable than aryl-aryl interactions and because perfluoroaryl units are more hydrophobic than are analogous aryl units. One mutant, Phe-10 --> F5-Phe, provides enhanced tertiary structural stability relative to the native sequence. The other six mutants analyzed caused a decrease in stability.
Woll
Matthew G
MG
Department of Chemistry and School of Pharmacy, University of Wisconsin, Madison, Wisconsin 53706, USA.
Hadley
Erik B
EB
Mecozzi
Sandro
S
Gellman
Samuel H
SH
D000595:Amino Acid Sequence; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics*; D010649:Phenylalanine / Q000235:genetics / Q000378:metabolism*; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
D011506:Proteins; D010649:Phenylalanine