Calculating pKa values in enzyme active sites

Protein Science

Volumn 12, Issue 9, 2003, Pages 1894-1901

  Nielsen, Jens Erik ^a   McCammon, J Andrew ^a  

^a San Diego   (United States)

Author keywords

Active site; Catalysis; Electrostatics; Enzyme; pKa calculation

Indexed keywords

PROTON;

ALGORITHM; ARTICLE; BIOCATALYST; CALCULATION; CATALYSIS; CRYSTAL STRUCTURE; ELECTRICITY; ENERGY; ENZYME ACTIVE SITE; GENOMICS; IONIZATION; PKA; PRIORITY JOURNAL; PROTON TRANSPORT; REACTION ANALYSIS; SOLVATION; X RAY ANALYSIS;

ALGORITHMS; ANIMALS; BACILLUS; BINDING SITES; CATALYSIS; CATALYTIC DOMAIN; CHICKENS; CRYSTALLOGRAPHY, X-RAY; ELECTROSTATICS; ENZYMES; GENOME; HYDROGEN-ION CONCENTRATION; MODELS, MOLECULAR; MURAMIDASE; OXYGEN; PROTEIN CONFORMATION; PROTONS; TIME FACTORS;

EID: 0042011188     PISSN: 09618368     EISSN: None     Source Type: Journal    
DOI: 10.1110/ps.03114903     Document Type: Article

References (44)

1. Alexov, E.G. and Gunner, M.R. 1997. Incorporating protein conformational flexibility into the calculation of pH-dependent protein properties. Biophys. J. 72: 2075-2093.
2. Antosiewicz, J., McCammon, J.A., and Gilson, M.K. 1994. Prediction of pH-dependent properties of proteins. J. Mol. Biol. 238: 415-436.
3. Baker, N.A., Sept, D., Joseph, S., Holst, M.J., and McCammon, J.A. 2001. Electrostatics of nanosystems: Application to microtubules and the ribosome. Proc. Natl. Acad. Sci. 98: 10037-10041.
4. Bashford, D. and Karplus, M. 1990. pKa's of ionizable groups in proteins: Atomic detail from a continuum electrostatic model. Biochemistry 29: 10219-10225.
5. Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov. I.N., and Bourne, P.E. 2000. The Protein Data Bank. Nucleic Acids Res. 28: 235-242.
6. Beroza, P., Fredkin, D.R., Okamura, M.Y., and Feher, G. 1991. Protonation of interacting residues in a protein by a Monte Carlo method: Application to lysozyme and the photosynthetic reaction center of Rhodobacter sphaeroides. Proc. Natl. Acad. Sci. 88: 5804-5808.
7. Bolon, D.N. and Mayo, S.L. 2001. Enzyme-like proteins by computational design. Proc. Natl. Acad. Sci. 98: 14274-14279.
8. Coutinho, P.M. and Henrissat, B. 1999. Carbohydrate-active enzymes: An integrated database approach. In Recent advances in carbohydrate bioengineering (eds. H.J. Gilbert et al.), pp. 3-12. The Royal Society of Chemistry, Cambridge, UK.
9. Dao-Pin, S., Liao, D.-I., and Remington, S.J. 1989. Electrostatic fields in the active sites of lysozymes. Proc. Natl. Acad. Sci. 86: 5361-5365.
10. Davies, G. and Henrissat, B. 1995. Structures and mechanisms of glycosyl hydrolases. Structure 3: 853-859.
11. Demchuk, E. and Wade, R.C. 1996. Improving the continuum dielectric approach to calculating pKas of ionizable groups in proteins. J. Phys. Chem. 100: 17373-17387.
12. Gilson, M.K. 1993. Multiple-site titration and molecular modeling: Two rapid methods for computing energies and forces for ionizable groups in proteins. Proteins 15: 266-282.
13. Jorgensen, W.L. and Tirado-Rives, J. 1988. The OPLS potential functions for proteins: Energy minimizations for crystals for cyclic peptides and crambin. J. Am. Chem. Soc. 110: 1657-1666.
14. Karshikoff, A. 1995. A simple algorithm for the calculation of multiple site titration curves. Protein Eng. 8: 243-248.
15. Klein, C., Hollender, J., Bender, H., and Schulz, G.E. 1992. Catalytic center of cyclodextrin glycosyltransferase derived from X-ray structure analysis combined with site-directed mutagenesis. Biochemistry 31: 8740-8746.
16. Knegtel, R.M., Strokopytov, B., Penninga, D., Faber, O.G., Rozeboom, H.J., Kalk, K.H., Dijkhuizen, L., and Dijkstra, B.W. 1995. Crystallographic studies of the interaction of cyclodextrin glycosyltransferase from Bacillus circulans strain 251 with natural substrates and products. J. Biol. Chem. 270: 29256-29264.
17. Lamotte-Brasseur, J., Lounnas, V., Raquet, X., and Wade, R.C. 1999. pKa calculations for class A β-lactamases: Influence of substrate binding. Protein Sci. 8: 404-409.
18. Lamotte-Brasseur, J., Dubus, A., and Wade, R.C. 2000. pK(a) calculations for class C β-lactamases: The role of Tyr-150. Proteins 40: 23-28.
19. Lee, F.S., Chu, Z.T., and Warshel, A. 1993. Microscopic and semimicroscopic calculations of electrostatic energies by the POLARIS and Enzymix programs. J. Comp. Chem. 14: 161-168.
20. Machius, M., Declerck, N., Huber, R., and Wiegand, G. 1998. Activation of Bacillus licheniformis α-amylase through a disorde→order transition of the substrate-binding site mediated by a calcium-sodium-calcium metal triad. Structure 6: 281-292.
21. Madura, J.D., Briggs, J.M., Wade, R.C., Davis, M.E., Luty, B.A., and McCammon, J.A. 1995. Electrostatics and diffusion of molecules in solution&emdash;Simulations with the University of Houston Brownian Dynamics Program. Comput. Phys. Commun. 91: 57-95.
22. McIntosh, L.P., Hand, G., Johnson, P.E., Joshi, M.D., Korner, M., Plesniak, L.A., Ziser, L., Wakarchuk, W.W., and Withers, S.G. 1996. The pKa of the general acid/base carboxyl group of a glycosidase cycles during catalysis: A 13C-NMR study of Bacillus circulans xylanase. Biochemistry 35: 9958-9966.
23. Mehler, E.L. and Guarnieri, F. 1999. A self-consistent, microenvironment modulated screened coulomb potential approximation to calculate pH-dependent electrostatic effects in proteins. Biophys. J. 77: 3-22.
24. Nicholls, A. and Honig, B. 1991. A rapid finite difference algorithm, utilizing successive over-relaxation to solve the Poisson-Boltzmann equation. J. Comp. Chem. 12: 435-445.
25. Nielsen, J.E. and Borchert, T.V. 2000. Protein engineering of bacterial α-amylases. Biochim. Biophys. Acta 1543: 253-274.
26. Nielsen, J.E. and McCammon. J.A. 2003. On the evaluation and optimisation of protein X-ray structures for pKa calculations. Protein Sci. 12: 313-326.
27. Nielsen, J.E. and Vriend. G. 2001. Optimizing the hydrogen-bond network in Poisson-Boltzmann equation-based pK(a) calculations. Proteins 43: 403-412.
28. Ondrechen, M.J., Clifton, J.G., and Ringe, D. 2001. THEMATICS: A simple computational predictor of enzyme function from structure. Proc. Natl. Acad. Sci. 98: 12473-12478.
29. Philips, D.C. 1967. The hen egg white lysozyme molecule. Proc. Natl. Acad. Sci. 57: 484-495.
30. Powell, K.A., Ramer, S.W., Del Cardayre, S.B., Stemmer, W.P., Tobin, M.B., Longchamp, P.F., and Huisman, G.W. 2001. Directed evolution and biocatalysis. Angew. Chem. Int. Ed. Engl. 40: 3948-3959.
31. Ramanadham, M., Sieker, L.C., and Jensen, L.H. 1990. Refinement of triclinic lysozyme: II. The method of stereochemically restrained least squares. Acta Crystallogr. B 46: 63-69.
32. Raquet, X., Lounnas, V., Lamotte-Brasseur, J., Frere, J.M., and Wade, R.C. 1997. pKa calculations for class A β-lactamases: Methodological and mechanistic implications. Biophys. J. 73: 2416-2426.
33. Rydberg, E.H., Li, C., Maurus, R., Overall, C.M., Brayer, G.D., and Withers, S.G. 2002. Mechanistic analyses of catalysis in human pancreatic α-amylase: Detailed kinetic and structural studies of mutants of three conserved carboxylic acids. Biochemistry 41: 4492-4502.
34. Sandberg, L. and Edholm, O. 1999. A fast and simple method to calculate protonation states in proteins. Proteins 36: 474-483.
35. Sham, Y.Y., Chu, Z.T., and Warshel, A. 1997. Consistent calculations of pKas of ionizable residues in proteins: Semimicroscopic and microscopic approaches. J. Phys. Chem. 101: 4458-4472.
36. Strokopytov, B., Penninga, D., Rozeboom, H.J., Kalk, K.H., Dijkhuizen, L., and Dijkstra, B.W. 1995. X-ray structure of cyclodextrin glycosyltransferase complexed with acarbose. Implications for the catalytic mechanism of glycosidases. Biochemistry 34: 2234-2240.
37. Tanford, C. and Roxby, R. 1972. Interpretation of protein titration curves. Application to lysozyme. Biochemistry 11: 2193-2198.
38. Uitdehaag, J.C., Mosi, R., Kalk, K.H., van der Veen, B.A., Dijkhuizen, L., Withers, S.G., and Dijkstra, B.W. 1999. X-ray structures along the reaction pathway of cyclodextrin glycosyltransferase elucidate catalysis in the α-amylase family. Nat. Struct. Biol. 6: 432-436.
39. van Vlijmen, H.W., Schaefer, M., and Karplus, M. 1998. Improving the accuracy of protein pKa calculations: Conformational averaging versus the average structure. Proteins 33: 145-158.
40. Vocadlo, D.J., Davies, G.J., Laine, R., and Withers, S.G. 2001. Catalysis by hen egg-white lysozyme proceeds via a covalent intermediate. Nature 412: 835-838.
41. Wakarchuk, W.W., Campbell, R.L., Sung, W.L., Davoodi, J., and Yaguchi, M. 1994. Mutational and crystallographic analyses of the active site residues of the Bacillus circulans xylanase. Protein Sci. 3: 467-475.
42. Warshel, A. 1981. Calculations of enzymatic reactions: Calculations of pKa, proton transfer reactions, and general acid catalysis reactions in enzymes. Biochemistry 20: 3167-3177.
43. Wlodek, S.T., Antosiewicz, J., and McCammon, J.A. 1997. Prediction of titration properties of structures of a protein derived from molecular dynamics trajectories. Protein Sci. 6: 373-382.
44. Yang, A.S., Gunner, M.R., Sampogna, R., Sharp, K., and Honig, B. 1993. On the calculation of pKas in proteins. Proteins 15: 252-265.