Development of hydrophobicity parameters for prenylated proteins.
We have determined hydrophobicity parameters for the side-chains of the prenyl thioether protein modifications, farnesyl-cysteine and geranylgeranyl-cysteine. Farnesyl-Cys is somewhat more hydrophobic than palmitoyl-Cys, but geranylgeranyl-Cys is more than two log(P) units more non-polar. These post-translational modifications represent the most hydrophobic residues yet described quantitatively. Furthermore, such modifications occur at the COOH-terminus which is generally methyl esterified. Loss of the terminal negative charge and formation of the ester proceeds with the gain of an additional 2.343 log(P) units of hydrophobicity. Clearly, COOH-terminal prenylation and esterification impart sufficient potential to render the terminus membrane bound. Thus, hydrophobicity parameters presented here for the prenylated amino acyl residues extend our understanding of these important physiological derivatives and enable computational analysis of proteins thus modified.
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Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Ohio State University, Columbus 43210-1291.
D000595:Amino Acid Sequence; D003545:Cysteine / Q000031:analogs & derivatives* / Q000737:chemistry; D004224:Diterpenes / Q000737:chemistry*; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
D004224:Diterpenes; D011506:Proteins; C065977:geranylgeranylcysteine; C057785:S-farnesylcysteine; D003545:Cysteine