A summary of the measured pK values of the ionizable groups in folded proteins

Protein Science

Volumn 18, Issue 1, 2009, Pages 247-251

  Grimsley, Gerald R ^a   Scholtz, J Martin ^a,b   Pace, C Nick ^a,b  

^a TEXAS A AND M HEALTH SCIENCE CENTER   (United States)

^b TEXAS A AND M UNIVERSITY   (United States)

Author keywords

NMR spectroscopy; Peptide model compounds; pH titration; pK values; Protein ionizable groups

Indexed keywords

ASPARTIC ACID; CYSTEINE; GLUTAMIC ACID; HISTIDINE; LYSINE;

ARTICLE; NUCLEAR MAGNETIC RESONANCE; PH MEASUREMENT; PRIORITY JOURNAL; PROTEIN FOLDING; PROTEIN INTERACTION; PROTEIN SYNTHESIS;

AMINO ACID SEQUENCE; AMINO ACIDS; ASPARTIC ACID; GLUTAMIC ACID; HISTIDINE; HYDROGEN-ION CONCENTRATION; ISOELECTRIC POINT; NUCLEAR MAGNETIC RESONANCE, BIOMOLECULAR; PROTEIN FOLDING; PROTEIN STRUCTURE, TERTIARY; PROTEINS; TITRIMETRY;

EID: 58149476769     PISSN: 09618368     EISSN: 1469896X     Source Type: Journal    
DOI: 10.1002/pro.19     Document Type: Article

References (47)

1. Thurlkill RL, Grimsley GR, Scholtz JM, Pace CN (2006) pK values of the ionizable groups of proteins. Protein Sci 15:1214-1218.
2. Nozaki Y, Tanford C (1967) Examination of titration behavior. Methods Enzymol 11:715-734.
3. Tollinger M, Crowhurst KA, Kay LE, Forman-Kay JD (2003) Site-specific contributions to the pH dependence of protein stability. Proc Natl Acad Sci USA 100:4545-4550.
4. Cho JH, Raleigh DP (2005) Mutational analysis demonstrates that specific electrostatic interactions can play a key role in the denatured state ensemble of proteins. J Mol Biol 353:174-185.
5. Marti DN (2005) Apparent pKa shifts of titratable residues at high denaturant concentration and the impact on protein stability. Biophys Chem 118:88-92.
6. Pujato M, Bracken C, Mancusso R, Cataldi M, Tasayco ML (2005) pH dependence of amide chemical shifts in natively disordered polypeptides detects medium-range interactions with ionizable residues. Biophys J 89:3293-3302.
7. Cho JH, Raleigh DP (2006) Electrostatic interactions in the denatured state and in the transition state for protein folding: effects of denatured state interactions on the analysis of transition state structure. J Mol Biol 359:1437-1446.
8. Pujato M, Navarro A, Versace R, Mancusso R, Ghose R, Tasayco ML (2006) The pH-dependence of amide chemical shift of Asp/Glu reflects its pKa in intrinsically disordered proteins with only local interactions. Biochim Biophys Acta 1764:1227-1233.
9. Matousek WM, Ciani B, Fitch CA, Garcia-Moreno EB, Kammerer RA, Alexandrescu AT (2007) Electrostatic contributions to the stability of the GCN4 leucine zipper structure. J Mol Biol 374:206-219.
10. Quijada J, Lopez G, Versace R, Ramirez L, Tasayco ML (2007) On the NMR analysis of pKa values in the unfolded state of proteins by extrapolation to zero denaturant. Biophys Chem 129:242-250.
11. Markley JL (1975) Observation of histidine residues in proteins by means of nuclear magnetic resonance spectroscopy. Acc Chem Res 8:70-80.
12. Matthew JB, Gurd FR, Garcia-Moreno B, Flanagan MA, March KL, Shire SJ (1985) pH-dependent processes in proteins. CRC Crit Rev Biochem 18:91-197.
13. Forsyth WR, Antosiewicz JM, Robertson AD (2002) Empirical relationships between protein structure and carboxyl pKa values in proteins. Proteins 48:388-403.
14. Giletto A, Pace CN (1999) Buried, charged, non-ion-paired aspartic acid 76 contributes favorably to the conformational stability of ribonuclease T1. Biochemistry 38:13379-13384.
15. Baran KL, Chimenti MS, Schlessman JL, Fitch CA, Herbst KJ, Garcia-Moreno BE (2008) Electrostatic effects in a network of polar and ionizable groups in staphylococcal nuclease. J Mol Biol 379:1045-1062.
16. Edgcomb SP, Murphy KP (2002) Variability in the pKa of histidine side-chains correlates with burial within proteins. Proteins 49:1-6.
17. Wisz MS, Hellinga HW (2003) An empirical model for electrostatic interactions in proteins incorporating multiple geometry-dependent dielectric constants. Proteins 51:360-377.
18. Li H, Robertson AD, Jensen JH (2005) Very fast empirical prediction and rationalization of protein pKa values. Proteins 61:704-721.
19. Antosiewicz J, McCammon JA, Gilson MK (1994) Prediction of pH-dependent properties of proteins. J Mol Biol 238:415-436.
20. Schutz CN, Warshel A (2001) What are the dielectric "constants" of proteins and how to validate electrostatic models? Proteins 44:400-417.
21. Gunner MR, Mao J, Song Y, Kim J (2006) Factors influencing the energetics of electron and proton transfers in proteins. What can be learned from calculations? Biochim Biophys Acta 1757:942-968.
22. Tanford C (1968) Protein denaturation. Adv Protein Chem 23:121-282.
23. Fersht A (1985) Enzyme structure and mechanism, 2nd ed. New York: W.H. Freeman, p 475.
24. Bartlett GJ, Porter CT, Borkakoti N, Thornton JM (2002) Analysis of catalytic residues in enzyme active sites. J Mol Biol 324:105-121.
25. Harris TK, Turner GJ (2002) Structural basis of perturbed pKa values of catalytic groups in enzyme active sites. IUBMB Life 53:85-98.
26. Huyghues-Despointes BM, Thurlkill RL, Daily MD, Schell D, Briggs JM, Antosiewicz JM, Pace CN, Scholtz JM (2003) pK values of histidine residues in ribonuclease Sa: effect of salt and net charge. J Mol Biol 325:1093-1105.
27. Laurents DV, Huyghues-Despointes BM, Bruix M, Thurlkill RL, Schell D, Newsom S, Grimsley GR, Shaw KL, Trevino S, Rico M, Briggs JM, Antosiewicz JM, Scholtz JM, Pace CN (2003) Charge-charge interactions are key determinants of the pK values of ionizable groups in ribonuclease Sa (pI = 3.5) and a basic variant (pI = 10.2). J Mol Biol 325:1077-1092.
28. Thurlkill RL, Grimsley GR, Scholtz JM, Pace CN (2006) Hydrogen bonding markedly reduces the pK of buried carboxyl groups in proteins. J Mol Biol 362:594-604.
29. Karp DA, Gittis AG, Stahley MR, Fitch CA, Stites WE, Garcia-Moreno EB (2007) High apparent dielectric constant inside a protein reflects structural reorganization coupled to the ionization of an internal Asp. Biophys J 92:2041-2053.
30. Anderson DE, Becktel WJ, Dahlquist FW (1990) pH-induced denaturation of proteins: a single salt bridge contributes 3-5 kcal/mol to the free energy of folding of T4 lysozyme. Biochemistry 29:2403-2408.
31. Chivers PT, Prehoda KE, Volkman BF, Kim BM, Markley JL, Raines RT (1997) Microscopic pKa values of Escherichia coli thioredoxin. Biochemistry 36:14985-14991.
32. Dyson HJ, Jeng MF, Tennant LL, Slaby I, Lindell M, Cui DS, Kuprin S, Holmgren A (1997) Effects of buried charged groups on cysteine thiol ionization and reactivity in Escherichia coli thioredoxin: structural and functional characterization of mutants of Asp 26 and Lys 57. Biochemistry 36:2622-2636.
33. Schreiber G, Frisch C, Fersht AR (1997) The role of Glu73 of barnase in catalysis and the binding of barstar. J Mol Biol 270:111-122.
34. Dwyer JJ, Gittis AG, Karp DA, Lattman EE, Spencer DS, Stites WE, Garcia-Moreno EB (2000) High apparent dielectric constants in the interior of a protein reflect water penetration. Biophys J 79:1610-1620.
35. Bushnell GW, Louie GV, Brayer GD (1990) High-resolution three-dimensional structure of horse heart cytochrome c. J Mol Biol 214:585-595.
36. Tishmack PA, Bashford D, Harms E, Van Etten RL (1997) Use of 1H NMR spectroscopy and computer simulations to analyze histidine pKa changes in a protein tyrosine phosphatase: experimental and theoretical determination of electrostatic properties in a small protein. Biochemistry 36:11984-11994.
37. Pinitglang S, Watts AB, Patel M, Reid JD, Noble MA, Gul S, Bokth A, Naeem A, Patel H, Thomas EW, Steedharan SK, Verma C, Brocklehurst K (1997) A classical enzyme active center motif lacks catalytic competence until modulated electrostatically. Biochemistry 36:9968-9982.
38. Tolbert BS, Tajc SG, Webb H, Snyder J, Nielsen JE, Miller BL, Basavappa R (2005) The active site cysteine of ubiquitin-conjugating enzymes has a significantly elevated pKa: functional implications. Biochemistry 44:16385-16391.
39. Lesser GJ, Rose GD (1990) Hydrophobicity of amino acid subgroups in proteins. Proteins 8:6-13.
40. Garcia-Moreno B, Dwyer JJ, Gittis AG, Lattman EE, Spencer DS, Stites WE (1997) Experimental measurement of the effective dielectric in the hydrophobic core of a protein. Biophys Chem 64:211-224.
41. Kesvatera T, Jonsson B, Thulin E, Linse S (1996) Measurement and modelling of sequence-specific pKa values of lysine residues in calbindin D9k. J Mol Biol 259:828-839.
42. Shaw KL, Grimsley GR, Yakovlev GI, Makarov AA, Pace CN (2001) The effect of net charge on the solubility, activity, and stability of ribonuclease Sa. Protein Sci 10:1206-1215.
43. Pace CN, Hebert EJ, Shaw KL, Schell D, Both V, Krajcikova D, Sevcik J, Wilson KS, Dauter Z, Hartley RW, Grimsley GR (1998) Conformational stability and thermodynamics of folding of ribonucleases Sa, Sa2 and Sa3. J Mol Biol 279:271-286.
44. Greenstein JP, Klemperer FW, Wyman J, Jr (1939) Physical chemistry of cystine peptides. J Biol Chem 129:681-692.
45. Schaller W, Robertson AD (1995) pH, ionic strength, and temperature dependences of ionization equilibria for the carboxyl groups in turkey ovomucoid third domain. Biochemistry 34:4714-4723.
46. Assadi-Porter FM, Fillingame RH (1995) Proton-translocating carboxyl of subunit c of F1Fo H(+)-ATP synthase: the unique environment suggested by the pKa determined by 1H NMR. Biochemistry 34:16186-16193.
47. Garner MH, Bogardt RA Jr, Gurd FR (1975) Determination of the pK values for the alpha-amino groups of human hemoglobin. J Biol Chem 250:4398-4404.