pK values of the ionizable groups of proteins

Authors

  • Richard L. Thurlkill,

    1. Department of Molecular and Cellular Medicine, Texas A&M University, System Health Science Center, College Station, Texas 77843, USA
    2. Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843, USA
    Current affiliation:
    1. Department of Chemistry and Biochemistry, Angelo State University, San Angelo, TX 76909.
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  • Gerald R. Grimsley,

    1. Department of Molecular and Cellular Medicine, Texas A&M University, System Health Science Center, College Station, Texas 77843, USA
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  • J. Martin Scholtz,

    1. Department of Molecular and Cellular Medicine, Texas A&M University, System Health Science Center, College Station, Texas 77843, USA
    2. Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843, USA
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  • C. Nick Pace

    Corresponding author
    1. Department of Molecular and Cellular Medicine, Texas A&M University, System Health Science Center, College Station, Texas 77843, USA
    2. Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843, USA
    • C. Nick Pace, Department of Molecular and Cellular Medicine, Texas A&M University, System Health Science Center, College Station, TX 77843, USA; fax: (979) 847-9481.
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Abstract

We have used potentiometric titrations to measure the pK values of the ionizable groups of proteins in alanine pentapeptides with appropriately blocked termini. These pentapeptides provide an improved model for the pK values of the ionizable groups in proteins. Our pK values determined in 0.1 M KCl at 25°C are: 3.67±0.03 (α-carboxyl), 3.67±0.04 (Asp), 4.25±0.05 (Glu), 6.54±0.04 (His), 8.00±0.03 (α-amino), 8.55±0.03 (Cys), 9.84±0.11 (Tyr), and 10.40±0.08 (Lys). The pK values of some groups differ from the Nozaki and Tanford (N&T) pK values often used in the literature: Asp (3.67 this work vs. 4.0 N&T); His (6.54 this work vs. 6.3 N&T); α-amino (8.00 this work vs. 7.5 N&T); Cys (8.55 this work vs. 9.5 N&T); and Tyr (9.84 this work vs. 9.6 N&T). Our pK values will be useful to those who study pK perturbations in folded and unfolded proteins, and to those who use theory to gain a better understanding of the factors that determine the pK values of the ionizable groups of proteins.

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