Understanding the pKa of redox cysteines: The key role of hydrogen bonding

Antioxidants and Redox Signaling

Volumn 18, Issue 1, 2013, Pages 94-127

  Roos, Goedele ^a,b,c   Foloppe, Nicolas ^d   Messens, Joris ^a,b,c  

^a VRIJE UNIVERSITEIT BRUSSEL   (Belgium)

^b DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

^c Brussels Center for Redox Biology   (Belgium)

^d Brussels Center for Redox Biology ^*  (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CYSTEINE; CYSTEINE SULFUR; THIOREDOXIN; UNCLASSIFIED DRUG;

CHEMICAL REACTION KINETICS; DIPOLE; HYDROGEN BOND; MOLECULAR INTERACTION; OXIDATION REDUCTION REACTION; PRIORITY JOURNAL; REVIEW; SOLVATION; STATIC ELECTRICITY; THEORETICAL MODEL; THERMODYNAMICS;

EID: 84868206533     PISSN: 15230864     EISSN: 15577716     Source Type: Journal    
DOI: 10.1089/ars.2012.4521     Document Type: Review

References (195)

1. Adman E, Watenpaugh KD, and Jensen LH. NH-S hydrogen bonds in Peptococcus aerogenes ferredoxin, Clos-tridium pasteurianum rubredoxin, and Chromatium high potential iron protein. Proc Natl Acad Sci USA 72: 4854-4858, 1975.
2. Alexov E, Mehler EL, Baker N, A MB, Huang Y, Milletti F, Erik Nielsen J, Farrell D, Carstensen T, Olsson MH, Shen JK, Warwicker J, Williams S, and Word JM. Progress in the prediction of pK(a) values in proteins. Proteins 79: 3260-3275, 2011.
3. Alexov EG and Gunner MR. Incorporating protein con-formational flexibility into the calculation of pH-dependent protein properties. Biophys J 74: 2075-2093, 1997.
4. Antosiewicz J, McCammon JA, and Gilson MK. Prediction of pH-dependent properties of proteins. J Mol Biol 238: 415-436, 1994.
5. Antosiewicz J, McCammon JA, and Gilson MK. The determinants of pKas in proteins. Biochemistry 35: 7819-7833, 1996.
6. Aqvist J, Luecke H, Quiocho FA, and Warshel A. Dipoles localized at helix termini of proteins stabilize charges. Proc Natl Acad Sci USA 88: 2026, 1991.
7. Armstrong RN. Structure, catalytic mechanism, and evolution of the glutathione transferases. Chem Res Toxicol 10: 2-18, 1997.
8. Aslund F, Berndt KD, and Holmgren A. Redox potentials of glutaredoxins and other thiol-disulfide oxidoreduc-tases of the thioredoxin superfamily determined by direct protein-protein redox equilibria. J Biol Chem 272: 30780-30786, 1997.
9. Aslund F, Ehn B, Miranda-Vizuete A, Pueyo C, and Holmgren A. Two additional glutaredoxins exist in Escher-ichia coli: glutaredoxin 3 is a hydrogen donor for ribonucle-otide reductase in a thioredoxin/glutaredoxin 1 double mutant. Proc Natl Acad Sci USA 91: 9813-9817, 1994.
10. Bacik JP and Hazes B. Crystal structures of a poxviral glutaredoxin in the oxidized and reduced states show re-dox-correlated structural changes. J Mol Biol 365: 1545-1558, 2007.
11. Barkay T, Miller SM, and Summers AO. Bacterial mercury resistance from atoms to ecosystems. FEMS Microbiol Rev 27: 355-384, 2003.
12. Bas DC, Rogers DM, and Jensen JH. Very fast prediction and rationalization of pKa values for protein-ligand complexes. Proteins 73: 765-783, 2008.
13. a's of Ionizable groups in proteins: Atomic detail from a continuum electrostatic model. Biochemistry 29: 10219-10225, 1990.
14. Benesch RE and Benesch R. The acid strength of the-SH Group in cysteine and related compounds. J Am Chem Soc 77: 5877-5881, 1955.
15. Bessette PH, Cotto JJ, Gilbert HF, and Georgiou G. In vivo and in vitro function of the Escherichia coli periplasmic cys-teine oxidoreductase DsbG. J Biol Chem 274: 7784-7792, 1999.
16. Billiet L, Geerlings P, Messens J, and Roos G. The thermodynamics of thiol sulfenylation. Free Radic Biol Med 52: 1473-1485, 2012.
17. Bulaj G, Kortemme T, and Goldenberg DP. Ionization-reactivity relationships for cysteine thiols in polypeptides. Biochemistry 37: 8965-8972, 1998.
18. Burley SK and Petsko GA. Aromatic-aromatic interaction: a mechanism of protein structure stabilization. Science 229: 23-28, 1985.
19. Carvalho AP, Fernandes PA, and Ramos MJ. Similarities and differences in the thioredoxin superfamily. Prog Bio-phys Mol Biol 91: 229-248, 2006.
20. Chen WJ, Graminski GF, and Armstrong RN. Dissection of the catalytic mechanism of isozyme 4-4 of glutathione S-transferase with alternative substrates. Biochemistry 27: 647-654, 1988.
21. Cheng Z, Arscott LD, Ballou DP, and Williams CH, Jr. The relationship of the redox potentials of thioredoxin and thioredoxin reductase from Drosophila melanogaster to the enzymatic mechanism: reduced thioredoxin is the reduc-tant of glutathione in Drosophila. Biochemistry 46: 7875-7885, 2007.
22. Cheng Z, Zhang J, Ballou DP, and Williams CH, Jr. Reactivity of thioredoxin as a protein thiol-disulfide oxidore-ductase. Chem Rev 111: 5768-5783, 2011.
23. Click TH and Kaminski GA. Reproducing basic pKa values for turkey ovomucoid third domain using a polarizable force field. J Phys Chem B 113: 7844-7850, 2009.
24. Collet JF and Messens J. Structure, function, and mechanism of thioredoxin proteins. Antioxid Redox Signal 13: 1205-1216, 2010.
25. Collet JF, Riemer J, Bader MW, and Bardwell JC. Recon-stitution of a disulfide isomerization system. J Biol Chem 277: 26886-26892, 2002.
26. CRC. Handbook of Chemistry and Physics. Florida: CRC Press, 1994.
27. Creighton TE. Proteins: Structures and Molecular Properties. New York: W.H. Freeman, 1993.
28. Crow A, Acheson RM, Le Brun NE, and Oubrie A. Structural basis of Redox-coupled protein substrate selection by the cytochrome c biosynthesis protein ResA. J Biol Chem 279: 23654-23660, 2004.
29. D'Ambrosio K, Pedone E, Langella E, De Simone G, Rossi M, Pedone C, and Bartolucci S. A novel member of the protein disulfide oxidoreductase family from Aeropyrum pernix K1: structure, function and electrostatics. J Mol Biol 362: 743-752, 2006.
30. Davies MN, Toseland CP, Moss DS, and Flower DR. Benchmarking pK(a) prediction. BMC biochemistry 7: 18, 2006.
31. as of ionizable groups in proteins. J Phys Chem 100: 17373-17387, 1996.
32. Depuydt M, Messens J, and Collet JF. How proteins form disulfide bonds. Antioxid Redox Signal 15: 49-66, 2011.
33. Desiraju GR and Steiner T. IUCr Monographs on Crystallography, Vol. 9. Oxford: Oxford University Press/International Union of Crystallography, 1999.
34. Dickhout JG, Carlisle RE, and Austin RC. Interrelationship between cardiac hypertrophy, heart failure, and chronic kidney disease: endoplasmic reticulum stress as a mediator of pathogenesis. Circ Res 108: 629-642, 2011.
35. Dillet V, Dyson HJ, and Bashford D. Calculations of electrostatic interactions and pKas in the active site of Escher-ichia coli thioredoxin. Biochemistry 37: 10298-10306, 1998.
36. Discola KF, de Oliveira MA, Rosa Cussiol JR, Monteiro G, Barcena JA, Porras P, Padilla CA, Guimaraes BG, and Netto LE. Structural aspects of the distinct biochemical properties of glutaredoxin 1 and glutaredoxin 2 from Saccharomyces cerevisiae. J Mol Biol 385: 889-901, 2009.
37. Donohue J. On N-H-S hydrogen bonds. J Mol Biol 45: 231-235, 1969.
38. Dyson HJ, Jeng MF, Tennant LL, Slaby I, Lindell M, Cui DS, Kuprin S, and Holmgren A. Effects of buried charged groups on cysteine thiol ionization and reactivity in Es-cherichia coli thioredoxin: structural and functional characterization of mutants of Asp 26 and Lys 57. Biochemistry 36: 2622-2636, 1997.
39. Dyson HJ, Tennant LL, and Holmgren A. Proton-transfer effects in the active-site region of Escherichia coli thioredoxin using two-dimensional 1H NMR. Biochemistry 30: 4262-4268, 1991.
40. El Hajjaji H, Dumoulin M, Matagne A, Colau D, Roos G, Messens J, and Collet JF. The zinc center influences the redox and thermodynamic properties of Escherichia coli thioredoxin 2. J Mol Biol 386: 60-71, 2009.
41. Ferrer-Sueta G, Manta B, Botti H, Radi R, Trujillo M, and Denicola A. Factors affecting protein thiol reactivity and specificity in peroxide reduction. Chem Res Toxicol 24: 434-450, 2011.
42. Fitch CA and Garcia-Moreno EB. Structure-based pKa calculations using continuum electrostatics methods. Curr Prot Bioinform 8.11.18.11.22, 2006.
43. Foloppe N and Nilsson L. The glutaredoxin-C-P-Y-C-motif: influence of peripheral residues. Structure 12: 289-300, 2004.
44. Foloppe N and Nilsson L. Stabilization of the catalytic thiolate in a mammalian glutaredoxin: structure, dynamics and electrostatics of reduced pig glutaredoxin and its mutants. J Mol Biol 372: 798-816, 2007.
45. Foloppe N, Sagemark J, Nordstrand K, Berndt KD, and Nilsson L. Structure, dynamics and electrostatics of the active site of glutaredoxin 3 from Escherichia coli: Comparison with functionally related proteins. J Mol Biol 310: 449-470, 2001.
46. Forman-Kay JD, Clore GM, and Gronenborn AM. Relationship between electrostatics and redox function in human thioredoxin: characterization of pH titration shifts using two-dimensional homo-and heteronuclear NMR. Biochemistry 31: 3442-3452, 1992.
47. Gan Z and Wells WW. Identification and reactivity of the catalytic site of pig liver thioltransferase. J Biol Chem 262: 6704-6797, 1987.
48. Gan Z-R, Sardana MK, Jacobs JW, and Polokoff MA. Yeast thioltransferase-the active site cysteines display differential reactivity. Arch Biochem Biophys 282: 110-115, 1990.
49. Gane PJ, Freedman RB, and Warwicker J. A molecular model for the redox potential difference between thior-edoxin and DsbA, based on electrostatics calculations. J Mol Biol 249: 376-387, 1995.
50. Georgescu RE, Alexov EG, and Gunner MR. Combining conformational flexibility and continuum electrostatics for calculating pK(a)s in proteins. Biophys J 83: 1731-1748, 2002.
51. Gilbert HF. Molecular and cellular aspects of thiol-disulfide exchange. Adv Enzymol Relat Areas Mol Biol 63: 69-172, 1990.
52. Gilson MK. Multiple-site titration and molecular modeling: two rapid methods for computing energies and forces for ionizable groups in proteins. Proteins 15: 266-282, 1993.
53. Gilson MK and Honig B. Calculation of the total electrostatic energy of a macromolecular system: solvation energies, binding energies, and conformational analysis. Proteins 4: 7-18, 1988.
54. Gilson MK and Honig BH. The dielectric constant of a folded protein. Biopolymers 25: 2097-2119, 1986.
55. Grauschopf U, Winther JR, Korber P, Zander T, Dallinger P, and Bardwell JC. Why is DsbA such an oxidizing disulfide catalyst? Cell 83: 947-955, 1995.
56. Gregoret LM, Rader SD, Fletterick RJ, and Cohen FE. Hydrogen bonds involving sulfur atoms in proteins. Proteins 9: 99-107, 1991.
57. Griffiths SW, King J, and Cooney CL. The reactivity and oxidation pathway of cysteine 232 in recombinant human alpha 1-antitrypsin. J Biol Chem 277: 25486-25492, 2002.
58. Gu Y, Kar T, and Scheiner S. Fundamental Properties of the C-H$$$O Interaction: Is it a True Hydrogen Bond? J Am Chem Soc 121: 9411-9422, 1999.
59. Gu Y, Singh SV, and Ji X. Residue R216 and catalytic efficiency of a murine class alpha glutathione S-transferase toward benzo[a]pyrene 7(R),8(S)-diol 9(S), 10(R)-epoxide. Biochemistry 39: 12552-12557, 2000.
60. Guddat LW, Bardwell JC, Glockshuber R, Huber-Wunderlich M, Zander T, and Martin JL. Structural analysis of three His32 mutants of DsbA: support for an electrostatic role of His32 in DsbA stability. Protein Sci 6: 1893-1900, 1997.
61. Harris TK and Turner GJ. Structural basis of perturbed pKa values of catalytic groups in enzyme active sites. IUBMB Life 53: 85-98, 2002.
62. Hatahet F and Ruddock LW. Protein disulfide isomerase: a critical evaluation of its function in disulfide bond formation. Antioxid Redox Signal 11: 2807-2850, 2009.
63. Hawkins HC and Freedman RB. The reactivities and ioni-zation properties of the active-site dithiol groups of mammalian protein disulphide-isomerase. Biochem J 275 (Pt 2): 335-339, 1991.
64. Hayes JD, Flanagan JU, and Jowsey IR. Glutathione trans-ferases. Annu Rev Pharmacol Toxicol 45: 51-88, 2005.
65. Hennecke J, Spleiss C, and Glockshuber R. Influence of acidic residues and the kink in the active-site helix on the properties of the disulfide oxidoreductase DsbA. J Biol Chem 272: 189-195, 1997.
66. Hol WG, van Duijnen PT, and Berendsen HJ. The alpha-helix dipole and the properties of proteins. Nature 273: 443-446, 1978.
67. Honig B and Nicholls A. Classical electrostatics in biology and chemistry. Science 268: 1144-1149, 1995.
68. Huber-Wunderlich M and Glockshuber R. A single dipep-tide sequence modulates the redox properties of a whole enzyme family. Fold Des 3: 161-171, 1998.
69. Hugo M, Turell L, Manta B, Botti H, Monteiro G, Netto LE, Alvarez B, Radi R, and Trujillo M. Thiol and sulfenic acid oxidation of AhpE, the one-cysteine peroxiredoxin from Mycobacterium tuberculosis: kinetics, acidity constants, and conformational dynamics. Biochemistry 48: 9416-9426, 2009.
70. Hunter CA and Sanders JKM. The Nature of p-p Interactions. J Am Chem Soc 112: 5525-5534, 1990.
71. Ingelman M, Nordlund P, and Eklund H. The structure of a reduced mutant T4 glutaredoxin. FEBS Lett 370: 209-211, 1995.
72. Iqbalsyah TM, Moutevelis E, Warwicker J, Errington N, and Doig AJ. The CXXC motif at the N terminus of an a-helical peptide. Protein Sci 15: 1945-1950, 2006.
73. Jacobi A, Huber-Wunderlich M, Hennecke J, and Glockshuber R. Elimination of all charged residues in the vicinity of the active-site helix of the disulfide oxidoreduc-tase DsbA. Influence of electrostatic interactions on stability and redox properties. J Biol Chem 272: 21692-21699, 1997.
74. Jao SC, English Ospina SM, Berdis AJ, Starke DW, Post CB, and Mieyal JJ. Computational and mutational analysis of human glutaredoxin (thioltransferase): probing the molecular basis of the low pKa of cysteine 22 and its role in catalysis. Biochemistry 45: 4785-4796, 2006.
75. Jeng MF, Campbell AP, Begley T, Holmgren A, Case DA, Wright PE, and Dyson HJ. High-resolution solution structures of oxidized and reduced Escherichia coli thioredoxin. Structure 2: 853-868, 1994.
76. Jeng MF, Holmgren A, and Dyson HJ. Proton sharing between cysteine thiols in Escherichia coli thioredoxin: implications for the mechanism of protein disulfide reduction. Biochemistry 34: 10101-10105, 1995.
77. Jensen KS, Hansen RE, and Winther JR. Kinetic and ther-modynamic aspects of cellular thiol-disulfide redox regulation. Antioxid Redox Signal 11: 1047-1058, 2009.
78. Ji X, von Rosenvinge EC, Johnson WW, Tomarev SI, Pia-tigorsky J, Armstrong RN, and Gilliland GL. Three-dimensional structure, catalytic properties, and evolution of a sigma class glutathione transferase from squid, a progenitor of the lens S-crystallins of cephalopods. Biochemistry 34: 5317-5328, 1995.
79. Jones DP and Go YM. Mapping the cysteine proteome: analysis of redox-sensing thiols. Curr Opin Chem Biol 15: 103-112, 2011.
80. Joshi HV and Meier MS. The effect of a peptide helix macrodipole on the pKa of an Asp side chain carboxylate. J Am Chem Soc 118: 12038-12044, 1996.
81. Kallis GB and Holmgren A. Differential reactivity of the functional sulfhydryl groups of cysteine-32 and cysteine-35 present in the reduced form of thioredoxin from Escherichia coli. J Biol Chem 255: 10261-10265, 1980.
82. Karala AR, Lappi AK, and Ruddock LW. Modulation of an active-site cysteine pKa allows PDI to act as a catalyst of both disulfide bond formation and isomerization. J Mol Biol 396: 883-892, 2010.
83. Kerr KA, Ashmore JP, and Koetzle TF. A neutron diffraction study of L-cysteine. Acta Cryst B31: 2022-2026, 1975.
84. Khandogin J and Brooks CL, 3rd. Constant pH molecular dynamics with proton tautomerism. Biophys J 89: 141-157, 2005.
85. Khare D, Alexander P, Antosiewicz J, Bryan P, Gilson M, and Orban J. pKa measurements from nuclear magnetic resonance for the B1 and B2 immunoglobulin G-binding domains of protein G: comparison with calculated values for nuclear magnetic resonance and X-ray structures. Biochemistry 36: 3580-3589, 1997.
86. Kolm RH, Sroga GE, and Mannervik B. Participation of the phenolic hydroxyl group of Tyr-8 in the catalytic mechanism of human glutathione transferase P1-1. Biochem J 285 (Pt 2): 537-540, 1992.
87. Kongsted J, Ryde U, Wydra J, and Jensen JH. Prediction and rationalization of the pH dependence of the activity and stability of family 11 xylanases. Biochemistry 46: 13581-13592, 2007.
88. Kortemme T and Creighton TE. Ionisation of cysteine residues at the termini of model alpha-helical peptides. Relevance to unusual thiol pKa values in proteins of the thioredoxin family. J Mol Biol 253: 799-812, 1995.
89. Koumanov A, Karshikoff A, Friis EP, and Borchert TV. Conformational averaging in pK calculations: improvement and limitations in prediction of ionization properties of proteins. J Phys Chem B 105: 9339-9344, 2001.
90. Koumanov A, Ruterjans H, and Karshikoff A. Continuum electrostatic analysis of irregular ionization and proton allocation in proteins. Proteins 46: 85-96, 2002.
91. Krause G and Holmgren A. Substitution of the conserved tryptophan 31 in Escherichia coli thioredoxin by site-directed mutagenesis and structure-function analysis. J Biol Chem 266: 4056-4066, 1991.
92. Krautwurst H, Berti M, Encinas MV, and Frey PA. Reaction of wild-type C365S, and C458S saccharomyces cerevisiae phosphoenolpyruvate carboxykinases with fluorescent io-doacetamide derivatives. Arch Biochem Biophys 327: 123-130, 1996.
93. Kroncke KD and Klotz LO. Zinc fingers as biologic redox switches? Antioxid Redox Signal 11: 1015-1027, 2009.
94. Lah N, Lah J, Zegers I, Wyns L, and Messens J. Specific potassium binding stabilizes pI258 arsenate reductase from Staphylococcus aureus. J Biol Chem 278: 24673-24679, 2003.
95. Lappi AK, Lensink MF, Alanen HI, Salo KE, Lobell M, Juffer AH, and Ruddock LW. A conserved arginine plays a role in the catalytic cycle of the protein disulphide isom-erases. J Mol Biol 335: 283-295, 2004.
96. Ledwidge R, Hong B, Dotsch V, and Miller SM. NmerA of Tn501 mercuric ion reductase: structural modulation of the pKa values of the metal binding cysteine thiols. Biochemistry 49: 8988-8998, 2010.
97. Lee AC and Crippen GM. Predicting pKa. J Chem Inf Model 49: 2013-2033, 2009.
98. Lewin A, Crow A, Hodson CT, Hederstedt L, and Le Brun NE. Effects of substitutions in the CXXC active-site motif of the extracytoplasmic thioredoxin ResA. Biochem J 414: 81-91, 2008.
99. Lewin A, Crow A, Oubrie A, and Le Brun NE. Molecular basis for specificity of the extracytoplasmic thioredoxin ResA. J Biol Chem 281: 35467-35477, 2006.
100. Li H, Hanson C, Fuchs JA, Woodward C, and Thomas GJ. Determination of the pKa values of active-center cysteines, cysteines-32 and-35, in Escherichia coli thioredoxin by Raman spectroscopy. Biochemistry 32: 5800-5808, 1993.
101. Li H, Robertson AD, and Jensen JH. The determinants of carboxyl pKa values in turkey ovomucoid third domain. Proteins 55: 689-704, 2004.
102. a values. Proteins 61: 704-721, 2005.
103. Li Y, Hu Y, Zhang X, Xu H, Lescop E, Xia B, and Jin C. Conformational fluctuations coupled to the thiol-disulfide transfer between thioredoxin and arsenate reductase in Bacillus subtilis. J Biol Chem 282: 11078-11083, 2007.
104. Liu S, Zhang P, Ji X, Johnson WW, Gilliland GL, and Armstrong RN. Contribution of tyrosine 6 to the catalytic mechanism of isoenzyme 3-3 of glutathione S-transferase. J Biol Chem 267: 4296-4299, 1992.
105. Loumaye E, Ferrer-Sueta G, Alvarez B, Rees JF, Clippe A, Knoops B, Radi R, and Trujillo M. Kinetic studies of per-oxiredoxin 6 from Arenicola marina: rapid oxidation by hydrogen peroxide and peroxynitrite but lack of reduction by hydrogen sulfide. Arch Biochem Biophys 514: 1-7, 2011.
106. Macedo MG, Anar B, Bronner IF, Cannella M, Squitieri F, Bonifati V, Hoogeveen A, Heutink P, and Rizzu P. The DJ-1L166P mutant protein associated with early onset Parkinson's disease is unstable and forms higher-order protein complexes. Hum Mol Genet 12: 2807-2816, 2003.
107. Marchal S and Branlant G. Evidence for the chemical activation of essential cys-302 upon cofactor binding to nonphosphorylating glyceraldehyde 3-phosphate dehy-drogenase from Streptococcus mutans. Biochemistry 38: 12950-12958, 1999.
108. Marino SM and Gladyshev VN. Cysteine function governs its conservation and degeneration and restricts its utilization on protein surfaces. J Mol Biol 404: 902-916, 2010.
109. Marino SM and Gladyshev VN. Analysis and functional prediction of reactive cysteine residues. J Biol Chem 287: 4419-4425, 2012.
110. Mason AC and Jensen JH. Protein-protein binding is often associated with changes in protonation state. Proteins 71: 81-91, 2008.
111. Mavridou DA, Stevens JM, Ferguson SJ, and Redfield C. Active-site properties of the oxidized and reduced C-terminal domain of DsbD obtained by NMR spectroscopy. J Mol Biol 370: 643-658, 2007.
112. Mavridou DA, Stevens JM, Goddard AD, Willis AC, Ferguson SJ, and Redfield C. Control of periplasmic inter-domain thiol:disulfide exchange in the transmembrane oxidoreductase DsbD. J Biol Chem 284: 3219-3226, 2009.
113. Messens J, Martins JC, Van Belle K, Brosens E, Desmyter A, De Gieter M, Wieruszeski JM, Willem R, Wyns L, and Ze-gers I. All intermediates of the arsenate reductase mechanism, including an intramolecular dynamic disulfide cascade. Proc Natl Acad Sci USA 99: 8506-8511, 2002.
114. Messens J, Van Molle I, Vanhaesebrouck P, Limbourg M, Van Belle K, Wahni K, Martins JC, Loris R, and Wyns L. How thioredoxin can reduce a buried disulphide bond. J Mol Biol 339: 527-537, 2004.
115. Mieyal JJ, Starke DW, Gravina SA, and Hocevar BA. Thioltransferase in human red blood cells: kinetics and equilibrium. Biochemistry 30: 8883-8891, 1991.
116. Mossner E, Huber-Wunderlich M, and Glockshuber R. Characterization of Escherichia coli thioredoxin variants mimicking the active-sites of other thiol/disulfide oxido-reductases. Protein Sci 7: 1233-1244, 1998.
117. Mossner E, Iwai H, and Glockshuber R. Influence of the pK(a) value of the buried, active-site cysteine on the redox properties of thioredoxin-like oxidoreductases. FEBS Lett 477: 21-26, 2000.
118. Moutevelis E and Warwicker J. Prediction of pKa and re-dox properties in the thioredoxin superfamily. Protein Sci 13: 2744-2752, 2004.
119. Naor MM and Jensen JH. Determinants of cysteine pKa values in creatine kinase and alpha1-antitrypsin. Proteins 57: 799-803, 2004.
120. Nelson JW and Creighton TE. Reactivity and ionization of the active site cysteine residues of DsbA, a protein required for disulfide bond formation in vivo. Biochemistry 33: 5974-5983, 1994.
121. Nelson KJ, Day AE, Zeng BB, King SB, and Poole LB. Isotope-coded, iodoacetamide-based reagent to determine individual cysteine pK(a) values by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Anal Biochem 375: 187-195, 2008.
122. Nielsen JE, Andersen KV, Honig B, Hooft RW, Klebe G, Vriend G, and Wade RC. Improving macromolecular electrostatics calculations. Protein Eng 12: 657-662, 1999.
123. Nielsen JE, Borchert TV, and Vriend G. The determinants of alpha-amylase pH-activity profiles. Protein Eng 14: 505-512, 2001.
124. Nielsen JE and McCammon JA. Calculating pKa values in enzyme active sites. Protein Sci 12: 1894-1901, 2003.
125. Nielsen JE and Vriend G. Optimizing the hydrogen-bond network in Poisson-Boltzmann equation-based pKa calculations. Proteins 43: 403-412, 2001.
126. Nielsen JW, Jensen KS, Hansen RE, Gotfredsen CH, and Winther Jr. A fluorescent probe which allows highly specific thiol labeling at low pH. Anal Biochem 421: 115-120, 2012.
127. Nilsson L and Karshikoff A. Multiple pH regime molecular dynamics simulation for pK calculations. PLoS One 6: e20116, 2011.
128. Nordstrand K, Aslund F, Meunier S, Holmgren A, Otting G, and Berndt KD. Direct NMR observation of the Cys-14 thiol proton of reduced Escherichia coli Glutaredoxin-3 supports the presence of an active site thiol-thiolate hydrogen bond. FEBS letters 449: 196-200, 1999.
129. Olsson HMM, Søndergaard CR, Rostkowski M, and Jensen JH. PROPKA3: Consistent treatment of internal and surface residues in empirical pKa predictions. J Chem Theory Com-put 7: 525-537, 2011.
130. Polgar L. Mercaptide-imidazolium ion-pair: the reactive nucleophile in papain catalysis. FEBS Lett 47: 15-18, 1974.
131. Porat A, Lillig CH, Johansson C, Fernandes AP, Nilsson L, Holmgren A, and Beckwith J. The reducing activity of glu-taredoxin 3 toward cytoplasmic substrate proteins is restricted by methionine 43. Biochemistry 46: 3366-3377, 2007.
132. Porter MA, Hall JR, Locke JC, Jensen JH, and Molina PA. Hydrogen bonding is the prime determinant of carboxyl pKa values at the N-termini of alpha-helices. Proteins 63: 621-635, 2006.
133. a values. J Biomol NMR 35: 39-51, 2006.
134. Presnell SR and Cohen FE. Topological distribution of four-alpha-helix bundles. Proc Natl Acad Sci USA 86: 6592-6596, 1989.
135. Qin J, Clore GM, and Gronenborn AM. The high-resolution three-dimensional solution structures of the oxidized and reduced states of human thioredoxin. Structure 2: 503-522, 1994.
136. Rablen PR, Lockman JW, and Jorgensen WL. Ab initio study of hydrogen-bonded complexes of small organic molecules with water. J Phys Chem A 102: 3782-3797, 1998.
137. Reckenfelderbaumer N and Krauth-Siegel RL. Catalytic properties, thiol pK value, and redox potential of Trypano-soma brucei tryparedoxin. J Biol Chem 277: 17548-17555, 2002.
138. Ren G, Stephan D, Xu Z, Zheng Y, Tang D, Harrison RS, Kurz M, Jarrott R, Shouldice SR, Hiniker A, Martin JL, Heras B, and Bardwell JC. Properties of the thioredoxin fold superfamily are modulated by a single amino acid residue. J Biol Chem 284: 10150-10159, 2009.
139. Roos G, Buts L, Van Belle K, Brosens E, Geerlings P, Loris R, Wyns L, and Messens J. Interplay between ion binding and catalysis in the thioredoxin-coupled arsenate reductase family. J Mol Biol 360: 826-838, 2006.
140. Roos G, Foloppe N, Van Laer K, Wyns L, Nilsson L, Geerlings P, and Messens J. How thioredoxin dissociates Its mixed disulfide. PloS Comp Biol 5: e1000461, 2009.
141. Roos G, Garcia-Pino A, Van Belle K, Brosens E, Wahni K, Vandenbussche G, Wyns L, Loris R, and Messens J. The conserved active site proline determines the reducing power of Staphylococcus aureus thioredoxin. J Mol Biol 368: 800-811, 2007.
142. Roos G, Loverix S, and Geerlings P. Origin of the pK(a) perturbation of N-terminal cysteine in alpha-and 3(10)-helices: a computational DFT study. J Phys Chem B 110: 557-562, 2006.
143. Roos G and Messens J. Protein sulfenic acid formation: from cellular damage to redox regulation. Free Radic Biol Med 51: 314-326, 2011.
144. Roos G, Messens J, Loverix S, Wyns L, and Geerlings P. A computational and conceptual DFT study on the Michaelis complex of pI258 arsenate reductase. Structural aspects and activation of the electrophile and nucleophile. J Phys Chem B 108: 17216-17225, 2004.
145. Ruddock LW, Hirst TR, and Freedman RB. pH-dependence of the dithiol-oxidizing activity of DsbA (a periplasmic protein thiol:disulphide oxidoreductase) and protein dis-ulphide-isomerase: studies with a novel simple peptide substrate. Biochem J 315 (Pt 3): 1001-1005, 1996.
146. Rullmann JA, Bellido MN, and van Duijnen PT. The active site of papain. All-atom study of interactions with protein matrix and solvent. J Mol Biol 206: 101-118, 1989.
147. Rushmore TH and Pickett CB. Glutathione S-transferases, structure, regulation, and therapeutic implications. J Biol Chem 268: 11475-11478, 1993.
148. Sanchez R, Riddle M, Woo J, and Momand J. Prediction of reversibly oxidized protein cysteine thiols using protein structure properties. Protein Sci 17: 473-481, 2008.
149. Sancho J, Serrano L, and Fersht AR. Histidine residues at the N-and C-termini of alpha-helices: perturbed pKas and protein stability. Biochemistry 31: 2253-2258, 1992.
150. Schlesinger P and Westley J. An expanded mechanism for rhodanese catalysis. J Biol Chem 249: 780-788, 1974.
151. Sengupta D, Behera RN, Smith JC, and Ullmann GM. The alpha helix dipole: screened out? Structure 13: 849-855, 2005.
152. Sham YY, Chu ZT, and Warshel A. Consistent calculations of pKa's of ionizable residues in proteins: Semi-microscopic and microscopic approaches. J Phys Chem B 101: 4458-4472, 1997.
153. Sharp K. Electrostatic interactions in macromolecules. Curr Opin Struct Biol 4: 234-239, 1994.
154. Shekhter T, Metanis N, Dawson PE, and Keinan E. A residue outside the active site CXXC motif regulates the catalytic efficiency of Glutaredoxin 3. Mol BioSyst 6: 241-248, 2010.
155. Sheridan RP, Levy RM, and Salemme FR. alpha-Helix di-pole model and electrostatic stabilization of 4-alpha-helical proteins. Proc Natl Acad Sci USA 79: 4545-4549, 1982.
156. Simonson T, Carlsson J, and Case DA. Proton binding to proteins: pK(a) calculations with explicit and implicit solvent models. J Am Chem Soc 126: 4167-4180, 2004.
157. Simonson T and Perahia D. Dielectric properties of proteins from simulations: tools and techniques. Comput Phys Com-mun 91: 291-303, 1995.
158. Simonson T and Perahia D. Internal and interfacial dielectric properties of cytochrome c from molecular dynamics in aqueous solution. Proc Natl Sci USA 92: 1082-1086, 1995.
159. Søndergaard CR, Olsson HMM, Rostkowski M, and Jensen JH. Improved treatment of ligands and coupling effects in empirical calculation and rationalization of pKa values. J Chem Theory Comput 7: 2284-2295, 2011.
160. Stirnimann CU, Rozhkova A, Grauschopf U, Bockmann RA, Glockshuber R, Capitani G, and Grutter MG. High-resolution structures of Escherichia coli cDsbD in different redox states: a combined crystallographic, biochemical and computational study. J Mol Biol 358: 829-845, 2006.
161. Subramanian S and Ross PD. The enthalpy of protolysis of liver alcohol dehydrogenase upon binding nicotinamide adenine dinucleotide. J Biol Chem 254: 7826-7830, 1979.
162. Sun XX and Wang CC. The N-terminal sequence (residues 1-65) is essential for dimerization, activities, and peptide binding of Escherichia coli DsbC. J Biol Chem 275: 22743-22749, 2000.
163. Szajewski RP and Whitesides GM. Rate constants and equilibrium constants for thiol-disulfide interchange reactions involving oxidized glutathione. J Am Chem Soc 102: 2011-2025, 1980.
164. Tajc SG, Tolbert BS, Basavappa R, and Miller BL. Direct determination of thiol pKa by isothermal titration micro-calorimetry. J Am Chem Soc 126: 10508-10509, 2004.
165. Takahashi N and Creighton TE. On the reactivity and ionization of the active site cysteine residues of Escherichia coli thioredoxin. Biochemistry 35: 8342-8353, 1996.
166. Taylor R and Kennard O. Crystallographic evidence for the existence of C-H.O, C-H.N, and C-H.Cl hydrogen bonds. J Am Chem Soc 104: 5063-5070, 1982.
167. Thomas KA, Smith GM, Thomas TB, and Feldmann RJ. Electronic distributions within protein phenylalanine aromatic rings are reflected by the three-dimensional oxygen atom environments. Proc Natl Acad Sci USA 79: 4843-4847, 1982.
168. Thurlkill RL, Grimsley GR, Scholtz JM, and Pace CN. pK values of the ionizable groups of proteins. Protein Sci 15: 1214-1218, 2006.
169. Ullmann GM, Noodleman L, and Case DA. Density functional calculation of p K(a) values and redox potentials in the bovine Rieske iron-sulfur protein. J Biol Inorg Chem 7: 632-639, 2002.
170. van Duijnen PT, Thole BT, and Hol WG. On the role of the active site helix in papain, an ab initio molecular orbital study. Biophys Chem 9: 273-280, 1979.
171. van Straaten M, Missiakas D, Raina S, and Darby NJ. The functional properties of DsbG, a thiol-disulfide oxidore-ductase from the periplasm of Escherichia coli. FEBS Lett 428: 255-258, 1998.
172. van Vlijmen HW, Schaefer M, and Karplus M. Improving the accuracy of protein pKa calculations: conformational averaging versus the average structure. Proteins 33: 145-158, 1998.
173. Vargas R, Garza D, Dixon A, and Hay BP. How strong is the Ca-H.O=C hydrogen bond? J Am Chem Soc 122: 4750-4755, 2000.
174. Villadangos AF, Van Belle K, Wahni K, Tamu Dufe V, Freitas S, Nur H, De Galan S, Gil JA, Collet JF, Mateos LM, and Messens J. Corynebacterium glutamicum survives arsenic stress with arsenate reductases coupled to two distinct re-dox mechanisms. Mol Microbiol 82: 998-1014, 2011.
175. Wada A. The alpha-helix as an electric macro-dipole. Adv Biophys 1-63, 1976.
176. Wang PF, McLeish MJ, Kneen MM, Lee G, and Kenyon GL. An unusually low pK(a) for Cys282 in the active site of human muscle creatine kinase. Biochemistry 40: 11698-11705, 2001.
177. Wang RW, Newton DJ, Huskey SE, McKeever BM, Pickett CB, and Lu AY. Site-directed mutagenesis of glutathione S-transferase YaYa. Important roles of tyrosine 9 and aspartic acid 101 in catalysis. J Biol Chem 267: 19866-19871, 1992.
178. a's and oxidising power for DsbA mutants. FEBS Lett 385: 105-108, 1996.
179. Warwicker J and Watson HC. Calculation of the electric potential in the active site cleft due to alpha-helix dipoles. J Mol Biol 157: 671-679, 1982.
180. Waters ML. Aromatic interactions in model systems. Curr Opin Chem Biol 6: 736-741, 2002.
181. Wennmohs F, Staemmler V, and Schindler M. Theoretical investigation of weak hydrogen bonds to sulfur. J Chem Phys 119: 3208-3218, 2003.
182. Winterbourn CC and Metodiewa D. Reactivity of biologically important thiol compounds with superoxide and hydrogen peroxide. Free Radic Biol Med 27: 322-328, 1999.
183. Witt AC, Lakshminarasimhan M, Remington BC, Hasim S, Pozharski E, and Wilson MA. Cysteine pKa depression by a protonated glutamic acid in human DJ-1. Biochemistry 47: 7430-7440, 2008.
184. Wlodek ST, Antosiewicz J, and McCammon JA. Prediction of titration properties of structures of a protein derived from molecular dynamics trajectories. Protein Sci 6: 373-382, 1997.
185. Woo HA, Jeong W, Chang TS, Park KJ, Park SJ, Yang JS, and Rhee SG. Reduction of cysteine sulfinic acid by sulfir-edoxin is specific to 2-cys peroxiredoxins. J Biol Chem 280: 3125-3128, 2005.
186. Xiao G, Liu S, Ji X, Johnson WW, Chen J, Parsons JF, Stevens WJ, Gilliland GL, and Armstrong RN. First-sphere and second-sphere electrostatic effects in the active site of a class mu gluthathione transferase. Biochemistry 35: 4753-4765, 1996.
187. as in Proteins. Proteins 15: 252-265, 1993.
188. Yang AS and Honig B. On the pH dependence of protein stability. J Mol Biol 231: 459-474, 1993.
189. Yang YF and Wells WW. Identification and characterization of the functional amino acids at the active center of pig liver thioltransferase by site-directed mutagenesis. J Biol Chem 266: 12759-12765, 1991.
190. Ye J, Cho SH, Fuselier J, Li W, Beckwith J, and Rapoport TA. Crystal structure of an unusual thioredoxin protein with a zinc finger domain. J Biol Chem 282: 34945-34951, 2007.
191. You TJ and Bashford D. Conformation and hydrogen ion titration of proteins: a continuum electrostatic model with conformational flexibility. Biophys J 69: 1721-1733, 1995.
192. Zapun A, Missiakas D, Raina S, and Creighton TE. Structural and functional characterization of DsbC, a protein involved in disulfide bond formation in Escherichia coli. Biochemistry 34: 5075-5089, 1995.
193. Zegers I, Martins JC, Willem R, Wyns L, and Messens J. Arsenate reductase from S. aureus plasmid pI258 is a phosphatase drafted for redox duty. Nat Struct Biol 8: 843-847, 2001.
194. Zheng F, Zhan C-G, and Ornstein RL. Theoretical determination of two structural forms of the active site in cadmium-containing phosphotriesterases. J Phys Chem B 106: 717-722, 2002.
195. Zhou P, Tian F, Lv F, and Shang Z. Geometric characteristics of hydrogen bonds involving sulfur atoms in proteins. Proteins 76: 151-163, 2009.