Protonation Changes upon Ligand Binding to Trypsin and Thrombin: Structural Interpretation Based on pKa Calculations and ITC Experiments

Journal of Molecular Biology

Volumn 367, Issue 5, 2007, Pages 1347-1356

  Czodrowski, Paul ^a   Sotriffer, Christoph A ^a   Klebe, Gerhard ^a  

^a PHILIPPS UNIVERSITY MARBURG   (Germany)

Author keywords

ITC; pKa values; Poisson Boltzmann; protonation states; serine proteases

Indexed keywords

HISTIDINE; LIGAND; THROMBIN; TRYPSIN;

ARTICLE; CALCULATION; CRYSTAL STRUCTURE; ENZYME ANALYSIS; ENZYME BINDING; ENZYME CONFORMATION; ENZYME KINETICS; ENZYME STRUCTURE; ISOTHERMAL TITRATION CALORIMETRY; LIGAND BINDING; MOLECULAR DYNAMICS; PKA; PRIORITY JOURNAL; PROTON TRANSPORT; STRUCTURE ANALYSIS; THERMODYNAMICS; X RAY CRYSTALLOGRAPHY;

EID: 33947119575     PISSN: 00222836     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jmb.2007.01.022     Document Type: Article

References (32)

1. Bashford D., and Karplus M. pKa's of ionizable groups in proteins: atomic detail from a continuum electrostatic model. Biochemistry 29 (1990) 10219-10225
2. Antosiewicz J., McCammon J.A., and Gilson M.K. Prediction of pH-dependent properties of proteins. J. Mol. Biol. 238 (1994) 415-436
3. Nielsen J.E., and Vriend G. Optimizing the hydrogen-bond network in Poisson-Boltzmann equation-based pka calculations. Proteins: Struct. Funct. Genet. 43 (2001) 403-412
4. Nielsen J.E., and McCammon J.A. Calculating pKa values in enzyme active sites. Protein Sci. 12 (2003) 1894-1901
5. Warshel A. Calculations of enzymic reactions: calculations of pKa, proton transfer reactions, and general acid catalysis reactions in enzymes. Biochemistry 20 (1981) 3167-3177
6. Warshel A., and Levitt M. Theoretical studies of enzymatic reactions: dielectric electrostatic and steric stabilization of the carbonium ion in the reaction of lysozyme. J. Mol. Biol. 103 (1976) 227-249
7. Warshel A., and Russell S.T. Calculations of electrostatic interactions in biological systems and in solutions. Quart. Rev. Biophys. 17 (1984) 283-422
8. Sham Y.Y., Chu Z.T., and Warshel A. Consistent calculations of pKa's of ionizable residues in proteins: semi-microscopic and macroscopic approaches. J. Phys. Chem. B 101 (1997) 4458-4472
9. Li H., Robertson A.D., and Jensen J.H. Very fast empirical prediction and rationalization of protein pKa values. Proteins: Struct. Funct. Genet. 61 (2005) 704-721
10. Wisz M.S., and Hellinga H.W. An empirical model for electrostatic interactions in proteins incorporating multiple geometry-dependent dielectric constants. Proteins: Struct. Funct. Genet. 51 (2003) 360-377
11. Mehler E.L., and Guarnieri F. A self-consistent, microenvironment modulated screened coulomb potential approximation to calculate pH-dependent electrostatic effects in proteins. Biophys. J. 77 (1997) 3-22
12. Czodrowski P., Dramburg I., Sotriffer C.A., and Klebe G. Development, validation and application of adapted PEOE charges to estimate pKa values of functional groups in protein-ligand complexes. Proteins: Struct. Funct. Genet. 65 (2006) 424-437
13. Dullweber F., Stubbs M.T., Musil D., Stürzebecher J., and Klebe G. Factorising ligand affinity: a combined thermodynamic and crystallographic study of trypsin and thrombin inhibition. J. Mol. Biol. 313 (2001) 593-614
14. Kesvatera T., Jonsson B., Thulin E., and Linse S. Ionization behavior of acidic residues in calbindin. Proteins: Struct. Funct. Genet. 37 (1999) 106-115
15. Yang A.S., Gunner M.R., Sampogna R., Sharp K., and Honig B. On the calculation of pKas in proteins. Proteins: Struct. Funct. Genet. 15 (1993) 252-265
16. Onufriev A., Case D.A., and Ullmann G.M. A novel view of pH titration in biomolecules. Biochemistry 40 (2001) 3413-3419
17. Bashford D., and Gerwert K. Electrostatic calculations of the pKa values of ionizable groups in bacteriorhodopsin. J. Mol. Biol. 224 (1992) 473-486
18. Carlson H.A., Briggs J.M., and McCammon J.A. Calculation of the pKa values for the ligands and side chains of Escherichia coli D-alanine:D-alanine ligase. J. Med. Chem. 42 (1999) 109-117
19. Klingen A.R., Bombarda E., and Ullmann M. Theoretical investigation of the behavior of titratable groups in proteins. Photochem. Photobiol. Sci. 6 (2006) 588-596
20. Trylska J., Antosiewicz J., Geller M., Hodge C.N., Klabe R.M., Head M.S., and Gilson M.K. Thermodynamic linkage between the binding of protons and inhibitors to HIV-1 protease. Protein Sci. 8 (1999) 180-195
21. Guvench O., Price D.J., and Brooks C.L. Receptor rigidity and ligand mobility in trypsin-ligand complexes. Proteins: Struct. Funct. Genet. 58 (2005) 407-417
22. Edgecomb S., and Murphy K. Variability in the pKa of histidine side-chains correlates with burial within proteins. Proteins: Struct. Funct. Genet. 49 (2002) 1-6
23. Plesniak L.A., Connelly G.P., Wakarchuk W.W., and McIntosh L.P. Characterization of a buried neutral histidine residue in bacillus circulans xylanase: NMR assignments, pH titration, and hydrogen exchange. Protein Sci. 5 (1996) 2319-2328
24. Tishmack P.A., Bashford D., Harms E., and Van Etten R.L. 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 (1997) 11984-11994
25. Anderson D.E., Becktel W.J., and Dahlquist F.W. 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 (1990) 2403-2408
26. Toseland C.P., McSparron H., Davies M.N., and Flower D.R. PPD v1.0-an integrated, web-accessible database of experimentally determined protein pKa values. Nucl. Acids Res. 34 (2006) 199-203
27. Kaslik G., Westler W.M., Graf L., and Markley J.L. Properties of the His57-Asp102 dyad of rat trypsin D189S in the zymogen, activated enzyme, and alpha1-proteinase inhibitor complexed forms. Arch. Biochem. Biophys 362 (1999) 254-264
28. Tanokura M. 1H-NMR study on the tautomerism of the imidazole ring of histidine residues: I. Microscopic pK values and molar ratios of tautomers in histidine-containing peptides. Biochim. Biophys. Acta 742 (1983) 576-585
29. Gerber P., and Müller K. MAB, a generally applicable molecular force field for structure modelling in medicinal chemistry. J. Comput. Aid. Mol. Des. 9 (1996) 251-268
30. Jones G., Willett P., and Glen R.C. Molecular recognition of receptor sites using a genetic algorithm with a description of desolvation. J. Mol. Biol. 245 (1995) 43-52
31. Bashford D. An object-oriented programming suite for electrostatic effects in biological molecules. In: Ishikawa Y., Oldehoeft R.R., Reynders J.V.W., and Tholburn M. (Eds). Scientific Computing in Object-oriented Parallel Environments vol. 1343 (1997), Springer, Berlin 233-240
32. Word J.M., Lovell S.C., Richardson J.S., and Richardson D.C. Asparagine and glutamine: using hydrogen atom contacts in the choice of side-chain amide orientation. J. Mol. Biol. 285 (1999) 1735-1747