Stabilization of the Catalytic Thiolate in a Mammalian Glutaredoxin: Structure, Dynamics and Electrostatics of Reduced Pig Glutaredoxin and its Mutants

Journal of Molecular Biology

Volumn 372, Issue 3, 2007, Pages 798-816

  Foloppe, Nicolas ^a   Nilsson, Lennart ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

Author keywords

C X X C; cysteine; electrostatics; molecular dynamics; pKa

Indexed keywords

CYSTEINE; GLUTAREDOXIN;

ARTICLE; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME STRUCTURE; HYDROGEN BOND; MOLECULAR DYNAMICS; MUTAGENESIS; NONHUMAN; OXIDATION REDUCTION STATE; PKA; PRIORITY JOURNAL; PROTEIN STABILITY;

MAMMALIA; SUIDAE;

EID: 34548264692     PISSN: 00222836     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jmb.2007.05.101     Document Type: Article

References (96)

1. Carvalho A.P., Fernandes P.A., and Ramos M.J. Similarities and differences in the thioredoxin superfamilly. Progr. Biophys. Mol. Biol. 91 (2006) 229-248
2. Martin J.L. Thioredoxin - a fold for all reasons. Structure 3 (1995) 245-250
3. Eklund H., Cambillau C., Sjöberg B.M., Holmgren A., Jörnvall H., Höög J.O., and Bränden C.I. Conformational and functional similarities between glutaredoxins and thioredoxins. EMBO J. 3 (1984) 1443-1449
4. Kallis G.-B., 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 (1980) 10261-10265
5. Gan Z., and Wells W.W. Identification and reactivity of the catalytic site of pig liver thioltransferase. J. Biol. Chem. 262 (1987) 6704-6797
6. Yang Y., and Wells W.W. Identification and characterization of the functional amino acids at the active center of pig liver thioltransferase by site-directed mutagenesis. J. Biol. Chem. 266 (1991) 12759-12765
7. Nelson J.W., and Creighton T.E. Reactivity and ionization of the active site cysteine residues of DsbA, a protein required for disulfide bond formation in vivo. Biochemistry 33 (1994) 5974-5983
8. aS in the active site of Escherichia coli thioredoxin. Biochemistry 37 (1998) 10298-10306
9. Nordstrand K., Åslund F., Meunier S., Holmgren A., Otting G., and Berndt K.D. 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 (1999) 196-200
10. Kortemme T., Darby N.J., and Creighton T.H. Electrostatic interactions in the active site of the N-terminal thioredoxin-like domain of protein disulfide isomerase. Biochemistry 35 (1996) 14503-14511
11. Jeng M.F., Holmgren A., and Dyson H.J. Proton sharing between cysteine thiols in Escherichia coli thioredoxin: implications for the mechanism of protein disulfide reduction. Biochemistry 34 (1995) 10101-10105
12. Dyson H.J., Jeng M.F., Tennant L.L., Slaby I., Lindell M., Cui D.S., et al. Effects of buried charged groups on cysteine thiol ionization and reactivity in Escherichia coli thioredoxin: structural and functional characterization of mutants of Asp26 and Lys57. Biochemistry 36 (1997) 2622-2636
13. Grauschopf U., Winther J.R., Korber P., Zander T., Dallinger P., and Bardwell J.C.A. Why is DsbA such an oxidizing disulfide catalyst?. Cell 83 (1995) 947-955
14. Szajewski R.P., and Whitesides G.M. Rate constants and equilibrium constants for thiol-disulfide interchange reactions involving oxidized glutathione. J. Am. Chem. Soc. 102 (1980) 2011-2026
15. Gilbert H.F. Molecular and cellular aspects of thiol-disulfide exchange. Advan. Enzymol. Related Areas Mol. Biol. 63 (1990) 69-172
16. Guddat L.W., Bardwell J.C.A., Glockshuber R., Huber-Wunderlich M., Zander T., and Martin J.L. Stuctural analysis of three His32 mutants of DsbA: support for an electrostatic role of His32 in DsbA stability. Protein Sci. 6 (1997) 1893-1900
17. Huber-Wunderlich M., and Glockshuber R. A single dipeptide sequence modulates the redox properties of a whole enzyme family. Fold. Des. 3 (1998) 161-171
18. 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 (1997) 189-195
19. Chivers P.T., Prehoda K.E., and Raines R.T. The CXXC motif: a rheostat in the active site. Biochemistry 36 (1997) 4061-4066
20. Fernandes A.P., and Holmgren A. Glutaredoxins: glutathione-dependent redox enzymes with functions far beyond a simple thioredoxin backup system. Antiox. Redox Signal. 6 (2004) 63-74
21. Gane P.J., Freedman R.B., and Warwicker J. A molecular model for the redox potential difference between thioredoxin and DsbA, based on electrostatic calculations. J. Mol. Biol. 249 (1995) 376-387
22. Moutevelis E., and Warwicker J. Prediction of pKa and redox properties in the thioredoxin superfamily. Protein Sci. 13 (2004) 2744-2752
23. Warwicker J. Modeling charge interactions and redox properties in DsbA. J. Biol. Chem. 273 (1998) 2501-2504
24. Jacobi A., Huber-Wunderlich M., Hennecke J., and Glockshuber R. Elimination of all charged residues in the vicinity of the acitive-site helix of the disulfide oxidoreductase DsbA. J. Biol. Chem. 272 (1997) 21692-21699
25. Foloppe N., Sagemark J., Nordstrand K., Berndt K. D., 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 (2001) 449-470
26. Foloppe N., and Nilsson L. The glutaredoxin -C-P-Y-C- motif: influence of peripheral residues. Structure 12 (2004) 289-300
27. a of cysteine 22 and its role in catalysis. Biochemistry 45 (2006) 4785-4796
28. Mössner E., Huber-Wunderlich M., and Glockshuber R. Characterization of Escherichia coli thioredoxin variants mimicking the active-sites of other thiol/disulfide oxidoreductases. Protein Sci. 7 (1998) 1233-1244
29. Jeng M.-F., Campbell A.P., Begley T., Holmgren A., Case D.A., Wright P.E., and Dyson H.J. High-resolution solution structures of oxidized and reduced Escherichia coli thioredoxin. Structure 2 (1994) 853-868
30. Qin J., Clore M., and Gronenborn A.M. The high-resolution three-dimentional solution structures of the oxidized and reduced states of human thioredoxin. Structure 2 (1994) 503-522
31. Weichsel A., Gasdaska J.R., Powis G., and Montfort W.R. Crystal structures of reduced, oxidized, and mutated human thioredoxins: evidence for a regulatory homodimer. Structure 4 (1996) 735-751
32. 1H n.m.r. assignments and determination of the three-dimensional structure of reduced Escherichia coli glutaredoxin. J. Mol. Biol. 221 (1991) 1311-1324
33. Xia T.-H., Bushweller J.H., Sodano T., Billeter M., Björnberg O., Holmgren A., and Wüthrich K. NMR structure of oxidized Escherichia coli glutaredoxin: comparison with reduced E. coli glutaredoxin and functionally related proteins. Protein Sci. 1 (1992) 310-321
34. Bushweller J.H., Åslund F., Wüthrich K., and Holmgren A. Structural and functional characterization of the mutant Escherichia coli glutaredoxin(C14→S) and its mixed disulfide with glutathione. Biochemistry 31 (1992) 9288-9293
35. Berardi M.J., and Bushweller J.H. Binding specificity and mechanistic insight into glutaredoxin-catalysed protein disulfide reduction. J. Mol. Biol. 292 (1999) 151-161
36. Ingelman M., Nordlund P., and Eklund H. The structure of a reduced mutant T4 glutaredoxin. FEBS Letters 370 (1995) 209-211
37. Nordstrand K., Åslund F., Holmgren A., Otting G., and Berndt K.D. NMR structure of Escherichia coli glutaredoxin 3-glutathione mixed disulfide complex: implications for the enzymatic mechanism. J. Mol. Biol. 286 (1999) 541-552
38. Nordstrand K., Sandström A., Åslund F., Holmgren A., Otting G., and Berndt K. NMR structure of oxidized glutaredoxin 3 from Escherichia coli. J. Mol. Biol. 303 (2000) 423-432
39. Sun C., Berardi M.J., and Bushweller J.H. The NMR solution structure of human glutaredoxin in the fully reduced form. J. Mol. Biol. 280 (1998) 687-701
40. Katti S.K., Robbins A.H., Yang Y., and Wells W.W. Crystal structure of thioltransferase at 2.2 Å resolution. Protein Sci. 4 (1995) 1998-2005
41. Xia B., Vlamis-Gardikas A., Holmgren A., Wüthrich K., Wright P.E., and Dyson H.J. Solution structure of Escherichia coli glutaredoxin-2 shows similarity to mammalian glutathione-S-transferases. J. Mol. Biol. 310 (2001) 907-918
42. Fladvad M., Bellanda M., Potamitou Fernandes A., Mammi S., Vlamis-Gardikas A., Holmgren A., and Sunnerhagen M. Molecular mapping of functionalities in the solution structure of reduced Grx4, a monothiol glutaredoxin from Escherichia coli. J. Biol. Chem. 280 (2005) 24553-24561
43. Bacik J.-P., and Hazes B. Crystal structures of a poxviral glutaredoxin in the oxidized and reduced states show redox-correlated structural changes. J. Mol. Biol. 365 (2007) 1545-1558
44. Guddat L.W., Bardwell J.C.A., and Martin J. Crystal structures of the reduced and oxydized DsbA: investigation of domain motion and thiolate stabilization. Structure 6 (1998) 757-767
45. Tian G., Xiang S., Noiva R., Lennarz W.J., and Schindelin H. The crystal structure of yeast protein disulfide isomerase suggests cooperativity between its active sites. Cell 124 (2006) 61-73
46. Wang Y., Amegbey G., and Wishart D.S. Solution structures of reduced and oxidized bacteriophage T4 glutaredoxin. J. Biomol. NMR 29 (2004) 85-90
47. Nielsen J.E., Andersen K.V., Honig B., Hooft R. W. W., Klebe G., Vriend G., and Wade R.C. Improving macromolecular electrostatics calculations. Protein Eng. 12 (1999) 657-662
48. a values. J. Biomol. NMR 35 (2006) 39-51
49. a's and oxidising power for DsbA mutants. FEBS Letters 385 (1996) 105-108
50. a values. Proteins: Struct. Funct. Genet. 61 (2005) 704-721
51. Porat A., Lillig C.H., Johansson C., Fernandes A.P., Nilsson L., Holmgren A., and Beckwith J. The reducing activity of glutaredoxin 3 towards cytoplasmic substrate proteins is restricted by methionine 43. Biochemistry 46 (2007) 3366-3377
52. Åqvist J., Luecke H., Quiocho F.A., and Warshel A. Dipoles localized at helix termini of proteins stabilize charges. Proc. Natl Acad. Sci. USA 88 (1991) 2026-2030
53. Sengupta D., Behera R.N., Smith J.C., and Ullmann G. M. The α helix dipole: screened out?. Structure 13 (2005) 849-855
54. Gan Z.R., and Wells W.W. Purification and properties of thioltransferase. J. Biol. Chem. 261 (1986) 996-1001
55. Gan Z.R., and Wells W.W. The primary structure of pig liver thioltransferase. J. Biol. Chem. 262 (1987) 6699-6703
56. Yang Y., Gan Z.R., and Wells W.W. Cloning and sequencing of the cDNA encoding pig liver thioltransferase. Gene 83 (1989) 339-346
57. Yang Y., and Wells W.W. High level expression of pig liver thioltransferase (Glutaredoxin) in Escherichia coli. J. Biol. Chem. 265 (1990) 589-593
58. Gan, A.R. (1987). Purification, Characterization, Primary Structure, and Catalytic Mechanism Studies of Pig Liver Thioltransferase. Doctoral dissertation, Michigan State University.
59. Mieyal J.J., Starke D.W., Gravina S.A., and Hocevar B. A. Thioltransferase in human red blood cells: kinetics and equilibrium. Biochemistry 30 (1991) 8883-8891
60. Daggett V. Long timescale simulations. Curr. Opin. Struct. Biol. 10 (2000) 160-164
61. Rablen P.R., Lockman J.W., and Jorgensen W.L. Ab initio study of hydrogen-bonded complexes of small organic molecules with water. J. Phys. Chem. ser. A 102 (1998) 3782-3797
62. Desiraju G.R., and Steiner T. The Weak Hydrogen Bond ín Structural Chemistry and Biology. IUCr Monographs on Crystallography vol. 9 (1999), Oxford Science Publications, Oxford
63. 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 (1982) 5063-5070
64. 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 (1999) 9411-9422
65. Hunter C.A., and Sanders J.K.M. The nature of π-π interactions. J. Am. Chem. Soc. 112 (1990) 5525-5534
66. Waters M.L. Aromatic interactions in model systems. Curr. Opin. Chem. Biol. 6 (2002) 736-741
67. Burley S.K., and Petsko G.A. Aromatic-aromatic interaction: a mechanism of protein structure stabilization. Science 229 (1985) 23-28
68. Hunter C.A., Singh J., and Thornton J.M. π-π interactions: the geometry and energetics of phenylalanine-phenylalanine interactions in proteins. J. Mol. Biol. 218 (1991) 837-846
69. Thomas K.A., Smith G.M., Thomas T.B., and Feldmann R.J. Electronic distributions within protein phenylalanine aromatic rings are reflected by the three-dimensional oxygen atom environments. Proc. Natl Acad. Sci. USA 79 (1982) 4843-4847
70. Levitt M., and Perutz M.F. Aromatic rings act as hydrogen bond acceptors. J. Mol. Biol. 201 (1988) 751-754
71. as of ionizable groups in proteins. J. Phys. Chem. 100 (1996) 17373-17387
72. Yang Y., Jao S., Nanduri S., Starke D.W., Mieyal J.J., and Quin J. Reactivity of the human thiol transferase (glutaredoxin) C7S, C25S, C78S, C82S mutant and NMR solution structure of its glutathionyl mixed disulfide intermediate reflect catalytic specificity. Biochemistry 37 (1998) 17145-17156
73. Åslund F., Ehn B., Miranda-Vizuete A., Pueyo C., and Holmgren A. Two additional glutaredoxins exist in Escherichia coli: glutaredoxin 3 is a hydrogen donor for ribonucleotide reductase in a thioredoxin/glutaredoxin 1 double mutant. Proc. Natl Acad. Sci. USA 91 (1994) 9813-9817
74. Eklund H., Gleason F.K., and Holmgren A. Structural and functional relations among thioredoxins of different species. Proteins: Struct. Funct. Genet. 11 (1991) 13-28
75. Holmgren A. Thioredoxin structure and mechanism: conformational changes on oxidation of the active-site sulfhydryls to a disulfide. Structure 3 (1995) 239-243
76. Brooks B.R., Bruccoleri R.E., Olafson B.D., States D.J., Swaminathan S., and Karplus M. CHARMM: a program for macromolecular energy, minimization and dynamics calculations. J. Comp. Chem. 4 (1983) 187-217
77. MacKerell Jr. A.D., Bashford D., Bellott M., Dunbrack Jr. R.L., Evanseck J.D., Field M.J., et al. All-atom empirical potential for molecular modeling and dynamics studies of proteins. J. Phys. Chem. ser. B 102 (1998) 3586-3616
78. Steinbach P.J., and Brooks B.R. New spherical-cutoff methods for long-range forces in macromolecular simulation. J. Comp. Chem. 15 (1994) 667-683
79. Beck D.A.C., Armen R.S., and Daggett V. Cutoff size need not strongly influence molecular dynamics results for solvated polypeptides. Biochemistry 44 (2005) 609-616
80. Norberg J., and Nilsson L. On the truncation of long-range electrostatic interactions in DNA. Biophys. J. 79 (2000) 1537-1553
81. Brünger A.T., and Karplus M. Polar hydrogens positions in proteins: empirical energy placement and neutron diffraction comparison. Proteins 4 (1988) 148-156
82. Jorgensen W.L., Chandrasekhar J., Madura J.D., Impey R.W., and Klein M.L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 79 (1983) 926-935
83. Reiher, W. E., III (1985). Theoretical Studies of Hydrogen Bonding. PhD thesis, Harvard University, Cambridge, MA.
84. van Gunsteren W.F., and Berendsen H.J.C. Algorithms for macromolecular dynamics and constraint dynamics. Mol. Phys. 34 (1977) 1311-1327
85. Donohue J. On N-⋯S hydrogen bonds. J. Mol. Biol. 45 (1969) 231-235
86. Adman E., Watenpaugh K.D., and Jensen L.H. NH⋯S Hydrogen bonds in Peptococcus aerogenes ferredoxin, Clostridium pasteurianum rubredoxin, and Chromatium high potential iron protein. Proc. Natl Acad. Sci. USA 72 (1975) 4854-4858
87. Gregoret L.-M., Rader S.D., Fletterick R.J., and Cohen F.E. Hydrogen bonds involving sulfur atoms in proteins. Proteins: Struct. Funct. Genet. 9 (1991) 99-107
88. Kerr K.A., and Ashmore J.P. A neutron diffraction study of L-cysteine. Acta Crystallog. sect. B 31 (1975) 2022-2026
89. Allen F.H., Bird C.M., Rowland R.S., and Raithby P. R. Hydrogen-bond acceptor and donor properties of divalent sulfur (Y-S-Z and R-S-H). Acta Crystallog. sect. B 53 (1997) 696-701
90. Markley J.L., Bax A., Arata Y., Hilbers C.W., Kaptein R., Sykes B.D., et al. Recommendations for the presentation of NMR structures of proteins and nucleic acids. J. Mol. Biol. 280 (1998) 933-952
91. as of ionizable groups in proteins: atomic detail from a continuum electrostatic model. Biochemistry 29 (1990) 10219-10225
92. as in Proteins. Proteins: Struct. Funct. Genet. 15 (1993) 252-265
93. Madura J.D., Briggs J.M., Wade R.C., Davis M.E., Luty B.A., Ilin A., et al. Electrostatics and diffusion of molecules in solution: simulations with the University of Houston Brownian Dynamics program. J. Comput. Phys. Commun. 91 (1995) 57-95
94. a calculations for class A β-Lactamases: methodological and mechanistic implications. Biophys. J. 73 (1997) 2416-2426
95. Gilson M.K., Sharp K.A., and Honig B.H. Calculating the electrostatic potential of molecules in solution: method and error assessment. J. Comp. Chem. 9 (1987) 327-335
96. Gilson M.K. Multiple-site titration and molecular modeling: two rapid methods for computing energies and forces for ionizable groups in proteins. Proteins: Struct. Funct. Genet. 15 (1993) 266-282