pH-Dependent Conformational Changes in Proteins and Their Effect on Experimental pKas: The Case of Nitrophorin 4

PLoS Computational Biology

Volumn 8, Issue 11, 2012, Pages

  Di Russo, Natali V ^a,b   Estrin, Dario A ^b   Martí, Marcelo A ^b   Roitberg, Adrian E ^a  

^a University of Florida ^*  (United States)

^b UNIVERSIDAD DE BUENOS AIRES   (Argentina)

Author keywords

[No Author keywords available]

Indexed keywords

MOLECULAR DYNAMICS; PROTEINS;

ACID-BASE BEHAVIOR; AMINO-ACIDS; APPARENT PK A; CONFORMATIONAL CHANGE; ENZYME CATALYSIS; NITROPHORIN-4; PH-DEPENDENT; PROTEINS STRUCTURES; SUBSTRATE PROTEINS; SUBSTRATE-BINDING;

CONFORMATIONS;

ASPARTIC ACID; CARRIER PROTEIN; NITROPHORIN 4; UNCLASSIFIED DRUG;

ARTICLE; CONFORMATIONAL TRANSITION; MOLECULAR DYNAMICS; MOLECULAR MODEL; PH; PKA; PROTEIN ANALYSIS; PROTEIN CONFORMATION; PROTEIN INTERACTION; STRUCTURE ANALYSIS;

EID: 84870659973     PISSN: 1553734X     EISSN: 15537358     Source Type: Journal    
DOI: 10.1371/journal.pcbi.1002761     Document Type: Article

References (71)

1. Grimsley GR, Scholtz JM, Pace CN, (2009) A summary of the measured pK values of the ionizable groups in folded proteins. Protein Sci 18: 247-251.
2. Kukić P, Farrell D, Søndergaard CR, Bjarnadottir U, Bradley J, et al. (2010) Improving the analysis of NMR spectra tracking pH-induced conformational changes: removing artefacts of the electric field on the NMR chemical shift. Proteins 78: 971-984.
3. Harris TK, Turner GJ, (2002) Structural Basis of Perturbed pKa Values of Catalytic Groups in Enzyme Active Sites. IUBMB Life 53: 85-98.
4. 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.
5. Srivastava J, Barber DL, Jacobson MP, (2007) Intracellular pH sensors: design principles and functional significance. Physiology 22: 30-39.
6. McIntosh LP, Hand G, Johnson PE, Joshi MD, Körner M, et al. (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.
7. Chivers PT, Prehoda KE, Volkman BF, Kim BM, Markley JL, et al. (1997) Microscopic pKa values of Escherichia coli thioredoxin. Biochemistry 36: 14985-14991.
8. Dwyer JJ, Gittis AG, Karp DA, Lattman EE, Spencer DS, et al. (2000) High apparent dielectric constants inthe interior of a protein reflect water penetration. Biophys J 79: 1610-1620.
9. Stites WE, Gittis AG, Lattman EE, Shortle D, (1991) In a staphylococcal nuclease mutant the side-chain of a lysine replacing valine 66 is fully buried in the hydrophobic core. J Mol Biol 221: 7-14.
10. Schutz CN, Warshel A, (2001) What Are the Dielectric "Constants" of Proteins and How To Validate Electrostatic Models? Proteins 44: 400-417.
11. Andersen JF, Ding XD, Balfour CA, Shokhireva TK, Champagne DE, et al. (2000) Kinetics and equilibria in ligand binding by nitrophorins 1-4: evidence for stabilization of a nitric oxide-ferriheme complex through a ligand-induced conformational trap. Biochemistry 39: 10118-10131.
12. Berry RE, Shokhirev MN, Ho AYW, Yang F, Shokhireva TK, et al. (2009) Effect of mutation of carboxyl side-chain amino acids near the heme on the midpoint potentials and ligand binding constants of nitrophorin 2 and its NO, histamine, and imidazole complexes. J Am Chem Soc 131: 2313-2327.
13. Chakrabarty S, Namslauer I, Brzezinski P, Warshel A, (2011) Exploration of the cytochrome c oxidase pathway puzzle and examination of the origin of elusive mutational effects. Biochim Biophys Acta 1807: 413-426.
14. Tanford C, (1961) Ionization-linked Changes in Protein Conformation. I. Theory. J Am Chem Soc 83: 1628-1634.
15. Wyman J, (1948) Heme Proteins. Adv Protein Chem 4: 407-531.
16. Yang A, Honig B, (1993) On the pH dependence of protein stability. J Mol Biol 231: 459-474.
17. Antosiewicz J, McCammon JA, Gilson MK, (1994) Prediction of pH-dependent properties of proteins. J Mol Biol 238: 415-436.
18. Bashford D, Karplus M, (1991) Multiple-site titration curves of proteins: an analysis of exact and approximate methods for their calculation. J Phys Chem 95: 9556-9561.
19. Georgescu RE, Alexov EG, Gunner MR, (2002) Combining conformational flexibility and continuum electrostatics for calculating pK(a)s in proteins. Biophys J 83: 1731-1748.
20. Alexov EG, Gunner MR, (1997) Incorporating protein conformational flexibility into the calculation of pH-dependent protein properties. Biophys J 72: 2075-2093.
21. Karp DA, Gittis AG, Stahley MR, Fitch CA, Stites WE, et al. (2007) High apparent dielectric constant inside a protein reflects structural reorganization coupled to the ionization of an internal Asp. Biophys J 92: 2041-2053.
22. Whitten ST, García-Moreno E B, Hilser VJ, (2005) Local conformational fluctuations can modulate the coupling between proton binding and global structural transitions in proteins. Proc Natl Acad Sci U S A 102: 4282-4287.
23. Montfort WR, Weichsel A, Andersen JF, (2000) Nitrophorins and related antihemostatic lipocalins from Rhodnius prolixus and other blood-sucking arthropods. Biochim Biophys Acta 1482: 110-118.
24. Kirchhoff LV, (1993) American trypanosomiasis (Chagas' disease)-a tropical disease now in the United States. N Engl J Med 329: 639-644.
25. Champagne DE, Nussenzveig RH, Ribeiro JMC, (1995) Purification, partial characterization, and cloning of nitric oxide-carrying heme proteins (nitrophorins) from salivary glands of the blood-sucking insect Rhodnius prolixus. J Biol Chem 270: 8691-5.
26. Andersen JF, Champagne DE, Weichsel A, Ribeiro JMC, Balfour CA, et al. (1997) Nitric oxide binding and crystallization of recombinant nitrophorin I, a nitric oxide transport protein from the blood-sucking bug Rhodnius prolixus. Biochemistry 36: 4423-4428.
27. Andersen JF, Montfort WR, (2000) The crystal structure of nitrophorin 2. A trifunctional antihemostatic protein from the saliva of Rhodnius prolixus. J Biol Chem 275: 30496-30503.
28. Andersen JF, Weichsel A, Balfour CA, Champagne DE, Montfort WR, (1998) The crystal structure of nitrophorin 4 at 1.5 A resolution: transport of nitric oxide by a lipocalin-based heme protein. Structure 6: 1315-1327.
29. Weichsel A, Andersen JF, Champagne DE, Walker FA, Montfort WR, (1998) Crystal structures of a nitric oxide transport protein from a blood-sucking insect. Nat Struct Mol Biol 5: 304-309.
30. Weichsel A, Andersen JF, Roberts SA, Montfort WR, (2000) Nitric oxide binding to nitrophorin 4 induces complete distal pocket burial. Nat Struct Mol Biol 7: 551-554.
31. Kondrashov DA, Roberts SA, Weichsel A, Montfort WR, (2004) Protein functional cycle viewed at atomic resolution: conformational change and mobility in nitrophorin 4 as a function of pH and NO binding. Biochemistry 43: 13637-13647.
32. Maes EM, Weichsel A, Andersen JF, Shepley D, Montfort WR, (2004) Role of binding site loops in controlling nitric oxide release: structure and kinetics of mutant forms of nitrophorin 4. Biochemistry 43: 6679-6690.
33. Martí MA, González Lebrero MC, Roitberg AE, Estrin DA, (2008) Bond or cage effect: how nitrophorins transport and release nitric oxide. J Am Chem Soc 130: 1611-1618.
34. Menyhárd DK, Keserü GM, (2005) Protonation state of Asp30 exerts crucial influence over surface loop rearrangements responsible for NO release in nitrophorin 4. FEBS Lett 579: 5392-5398.
35. Martí MA, Estrin DA, Roitberg AE, (2009) Molecular basis for the pH dependent structural transition of Nitrophorin 4. J Phys Chem B113: 2135-2142.
36. Mongan J, Case DA, McCammon JA, (2004) Constant pH molecular dynamics in generalized Born implicit solvent. J Comput Chem 25: 2038-2048.
37. Baran KL, Chimenti MS, Schlessman JL, Fitch C, Herbst KJ, et al. (2008) Electrostatic effects in a network of polar and ionizable groups in staphylococcal nuclease. J Mol Biol 379: 1045-1062.
38. Kato M, Warshel A, (2006) Using a charging coordinate in studies of ionization induced partial unfolding. J Phys Chem B 110: 11566-11570.
39. Damjanović A, Wu X, García-Moreno EB, Brooks BR, (2008) Backbone relaxation coupled to the ionization of internal groups in proteins: a self-guided Langevin dynamics study. Biophys J 95: 4091-4101.
40. Baptista AM, Teixeira VH, Soares CM, (2002) Constant-pH molecular dynamics using stochastic titration. J Chem Phys 117: 4184-4200.
41. Walczak AM, Antosiewicz JM, (2002) Langevin Dynamics of Proteins at Constant pH. Phys Rev E Stat Nonlin Soft Matter Phys 66: 051911/1-051911/8.
42. Lee MS, Salsbury FR, Brooks CLI, (2004) Constant-pH molecular dynamics using continuous titration coordinates. Proteins 56: 738-752.
43. Khandogin J, Brooks CL, (2005) Constant pH molecular dynamics with proton tautomerism. Biophys J 89: 141-157.
44. Shi C, Wallace JA, Shen JK, (2012) Thermodynamic Coupling of Protonation and Conformational Equilibria in Proteins: Theory and Simulation. Biophys J 102: 1590-1597.
45. Maes EM, Roberts SA, Weichsel A, Montfort WR, (2005) Ultrahigh resolution structures of nitrophorin 4: heme distortion in ferrous CO and NO complexes. Biochemistry 44: 12690-12699.
46. Nienhaus K, Maes EM, Weichsel A, Montfort WR, Nienhaus GU, (2004) Structural dynamics controls nitric oxide affinity in nitrophorin 4. J Biol Chem 279: 39401-39407.
47. Abbruzzetti S, He C, Ogata H, Bruno S, Viappiani C, et al. (2012) Heterogeneous kinetics of the carbon monoxide association and dissociation reaction of nitrophorin 4 and 7 coincide with structural heterogeneity of the gate-loop. J Am Chem Soc 134: 9986-9998.
48. Benabbas A, Ye X, Kubo M, Zhang Z, Maes EM, et al. (2010) Ultrafast dynamics of diatomic ligand binding to nitrophorin 4. J Am Chem Soc 132: 2811-2820.
49. Swails JM, Meng Y, Walker FA, Martí MA, Estrin DA, et al. (2009) pH-dependent mechanism of nitric oxide release in nitrophorins 2 and 4. J Phys Chem B 113: 1192-1201.
50. Ogata H, Knipp M, (2012) Crystallization and preliminary X-ray crystallographic analysis of the membrane-binding haemprotein nitrophorin 7 from Rhodnius prolixus. Acta Cryst Sect F Struct Biol Cryst Commun 68: 37-40.
51. Tanford C, Bunville LG, Nozaki Y, (1959) Reversible transformation of β-lactoglobulin at pH 7.5. J Am Chem Soc 81: 4032-4036.
52. Tanford C, Taggart VG, (1961) Ionization-linked Changes in Protein Conformation. II. The N→R transition in β-lactoglobulin. J Am Chem Soc 83: 1634-1638.
53. Qin BY, Bewley MC, Creamer LK, Baker HM, Baker EN, et al. (1998) Structural basis of the Tanford transition of bovine beta-lactoglobulin. Biochemistry 37: 14014-14023.
54. Seeger MA, vonBallmoos C, Verrey F, Pos KM, (2009) Crucial role of Asp408 in the proton translocation pathway of multidrug transporter AcrB: evidence from site-directed mutagenesis and carbodiimide labeling. Biochemistry 48: 5801-5812.
55. Murakami S, Nakashima R, Yamashita E, Matsumoto T, Yamaguchi A, (2006) Crystal structures of a multidrug transporter reveal a functionally rotating mechanism. Nature 443: 173-179.
56. Olkhova E, Hunte C, Screpanti E, Padan E, Michel H, (2006) Multiconformation continuum electrostatics analysis of the NhaA Na+/H+ antiporter of Escherichia coli with functional implications. Proc Natl Acad Sci U S A 103: 2629-2634.
57. Kluge C, Dimroth P, (1993) Kinetics of Inactivation of the F1F0 ATPase of Propionigenium modestum by Dicyclohexylcarbodiimide in Relationship to H+ and Na+ Concentration: Probing the Binding Site for the Coupling Ions. Biochemistry 32: 10378-10386.
58. Assadi-Porter FM, Fillingame RH, (1995) Proton-Translocating Carboxyl of Subunit c of F1F0- H+ ATP Synthas: The Unique Environment Suggested by the pKa determined by 1H NMR. Biochemistry 34: 16186-16193.
59. Rivera-Torres IO, Krueger-Koplin RD, Hicks DB, Cahill SM, Krulwich TA, et al. (2004) pKa of the essential Glu54 and backbone conformation for subunit c from the H+-coupled F1F0 ATP synthase from an alkaliphilic Bacillus. FEBS Lett 575: 131-5.
60. Webb H, Tynan-Connolly BM, Lee GM, Farrell D, O'Meara F, et al. (2011) Re-measuring HEWL pKa values by NMR spectroscopy: Methods, analysis, accuracy and implications for theoretical pKa calculations. Proteins 79: 685-702.
61. Garel JR, Epely S, Labouesse B, (1974) The Acidic Transition of δ-Chymotrypsin. Biochemistry 13: 3117-3123.
62. Garel JR, Labouesse B, (1971) Rate of ligand-promoted isomerization of proteins. Relaxation study of the "alkaline-transition" of δ-chymotrypsin. Biochimie 53: 9-16.
63. McPhie P, (1979) The Alkaline Transition of Swine Pepsinogen. Biophys Chem 9: 281-287.
64. Fersht AR, (1972) Conformational Equilibria in alpha and delta Chymotrypsin. J Mol Biol 64: 497-509.
65. Xiang T, Liu F, Grant DM, (1991) Generalized Langevin equations for molecular dynamics in solution. J Chem Phys 94: 4463-4471.
66. Ryckaert JP, Ciccotti G, Berendsen HJC, (1977) Numerical integration of the Cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes. J Comput Phys 23: 327-341.
67. Hornak V, Abel R, Okur A, Strockbine B, Roitberg AE, et al. (2006) Comparison of Multiple Amber Force Fields and Development of Improved Protein Backbone Parameters. Proteins 725: 712-725.
68. Bikiel DE, Boechi L, Capece L, Crespo A, De Biase PM, et al. (2006) Modeling heme proteins using atomistic simulations. Phys Chem Chem Phys 8: 5611-5628.
69. Case DA, Darden TA, Cheatham TE, Simmerling CL, Wang J, et al. (2010) AMBER 11. University of California, San Francisco (San Francisco).
70. Onufriev A, Bashford D, Case DA, (2004) Exploring protein native states and large-scale conformational changes with a modified generalized born model. Proteins 55: 383-394.
71. Metropolis N, Rosenbluth AW, Rosenbluth MN, Teller AH, Teller E, (1953) Equation-of-state calculations by fast computing machines. J Chem Phys 21: 1087-1092.