Dynamic Regulation of Phenylalanine Hydroxylase by Simulated Redox Manipulation

PLoS ONE

Volumn 7, Issue 12, 2012, Pages

  Fuchs, Julian E ^a   Huber, Roland G ^a   von Grafenstein, Susanne ^a   Wallnoefer, Hannes G ^a   Spitzer, Gudrun M ^a   Fuchs, Dietmar ^b   Liedl, Klaus R ^a  

^a UNIVERSITY OF INNSBRUCK   (Austria)

^b INNSBRUCK MEDICAL UNIVERSITY   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

CYSTEINE; PHENYLALANINE 4 MONOOXYGENASE; TYROSINE;

ARTICLE; CONFORMATIONAL TRANSITION; ENZYME METABOLISM; ENZYME REGULATION; MOLECULAR DYNAMICS; OXIDATION REDUCTION REACTION; OXIDATIVE STRESS; SIMULATION;

CATALYTIC DOMAIN; MODELS, MOLECULAR; OXIDATION-REDUCTION; PHENYLALANINE HYDROXYLASE; PROTEIN CONFORMATION; SUBSTRATE SPECIFICITY;

EID: 84871724352     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0053005     Document Type: Article

References (73)

1. Werner ER, Blau N, Thöny B, (2011) Tetrahydrobiopterin: Biochemistry and Pathophysiology. Biochem J 438: 397-414.
2. Kaufman S, Holtzman NA, Milstien S, Butler IJ, Krumholz A, (1975) Phenylketonuria Due to a Deficiency of Dihydrobiopteridine Reductase. N Engl J Med 293: 785-790.
3. Blau N, Van Spronsen FJ, Levy HL, (2010) Phenylketonuria. Lancet 376: 1417-1427.
4. Scriver CR, Hurtubise M, Konecki D, Phommorinh M, Prevost L, et al. (2003) PAHdb 2003: What a Locus-Specific Knowledgebase Can Do. Hum Mutat 21: 333-344.
5. Folling A, (1934) Ueber Ausscheidung von Phenylbrenztraubensaeure in den Harn als Stoffwechselanomalie in Verbindung mit Imbezillitaet. Ztschr Physiol Chem 227: 169-176.
6. Fitzpatrick PF, (2003) Mechanism of Aromatic Amino Acid Hydroxylation. Biochemistry 42: 14083-14091.
7. Olsson E, Martinez A, Teigen K, Jensen VR, (2011) Formation of the Iron-Oxo Hydroxylating Species in the Catalytic Cycle of Aromatic Amino Acid Hydroxylases. Chem Eur J 17: 3746-3758.
8. Olsson E, Martinez A, Teigen K, Jensen VR, (2011) Substrate hydroxylation by the Oxido-Iron Intermediate in Aromatic Amino Acid Hydroxylases: A DFT Mechanistic Study. Eur J Inorg Chem 17: 2720-2732.
9. Panay AJ, Lee M, Krebs C, Bollinger JM, Fitzpatrick PF, (2011) Evidence for a High-Spin Fe(IV) Species in the Catalytic Cycle of a Bacterial Phenylalanine Hydroxylase. Biochemistry 50: 1928-1933.
10. Erlandsen H, Fusetti F, Martinez A, Hough E, Flatmark T, et al. (1997) Crystal Structure of the Catalytic Domain of Human Phenylalanine Hydroxylase Reveals the Structural Basis for Phenylketonuria. Nat Struct Biol 4: 995-1000.
11. Fusetti F, Erlandsen H, Flatmark T, Stevens RC, (1998) Structure of Tetrameric Human Phenylalanine Hydroxylase and Its Implications for Phenylketonuria. J Biol Chem 273: 16962-16967.
12. Mitnaul LJ, Shiman R, (1995) Coordinate Regulation of Tetrahydrobiopterin Turnover and Phenylalanine Hydroxylase Activity in Rat Liver Cells. Proc Nastl Acad Sci USA 92: 885-889.
13. Abita JP, Milstien S, Chang N, Kaufman S, (1976) In Vitro Activation of Rat Liver Phenylalanine Hydroxylase by Phosphorylation. J Biol Chem 17: 5310-5314.
14. Shiman R, Mortimore GE, Schworer CM, Gray DW, (1982) Regulation of Phenylalanine Hydroxylase Activity by Phenylalanine in Vivo, in Vitro, and in Perfused Rat Liver. J Biol Chem 257: 11213-11216.
15. Shiman R, Gray DW, (1980) Substrate Activation of Phenylalanine Hydroxylase. J Biol Chem 255: 4793-4800.
16. Fitzpatrick PF, (1999) Tetrahydropterin-Dependent Amino Acid Hydroxylases. Annu Rev Biochem 68: 355-381.
17. Scriver CR, Kaufman S (2001) Hyperphenylalaninemia: phenylalanine hydroxylase deficiency. In: Scriver CR, Beaudet AL, Valle D, Sly WS, editors. The metabolic and molecular basis of inherited disease, 8th edition. 1667-1724.
18. Ronau JA, Abu-Omar MM, Das C (2012) Crystallographic characterization of a substrate-bindin site distinct from the active site in a bacterial phenylalanine hydroxylase. To be published, PDB: 3TCY.
19. Daubner SC, Hillas PJ, Fitzpatrick PF, (1997) Expression and Characterization of the Catalytic Domain of Human Phenylalanine Hydroxylase. Arch Biochem Biophys 348: 295-302.
20. Kobe B, Jennings IG, House CM, Michaell BJ, Goodwill KE, et al. (1999) Structural basis of autoregulation of phenylalanine hydroxylase. Nat Struct Biol 6: 442-448.
21. Miranda FF, Teigen K, Thorolfsson M, Svebak RM, Knappskog PM, et al. (2002) Phosphorylation and Mutations of Ser16 in Human Phenylalanine Hydroxylase. J Biol Chem 277: 40937-40943.
22. Jennings IG, Teh T, Kobe B, (2001) Essential Role of the N-terminal Autoregulatory Sequence in the Regulation of Phenylalanine Hydroxylase. FEBS Lett 488: 196-200.
23. Ploder M, Neurauter G, Spittler A, Schroecksnadel K, Roth E, et al. (2008) Serum phenylalanine in patients post trauma and with sepsis correlate to neopterin concentrations. Amino Acids 35: 303-307.
24. Neurauter G, Grahmann AV, Klieber M, Zeimet A, Ledochowski M, et al. (2008) Serum phenylalanine concentrations in patients with ovarian carcinoma correlate with concentrations of immune activation markers and of isoprostane-8. Cancer Lett 272: 141-147.
25. Zangerle R, Kurz K, Neurauter G, Kitchen M, Sarcletti M, et al. (2010) Increased blood phenylalanine to tyrosine ratio in HIV-1 infection and correction following effective antiretroviral therapy. Brain Behav Immun 24: 403-408.
26. Rosenblatt D, Scriver CR, (1968) Heterogeneity in Genetic Control of Phenylalanine Metabolism in Man. Nature 218: 677-678.
27. Zoller H, Schloegel A, Schroecksnadel S, Vogel W, Fuchs D, et al. (2012) Interferon-Alpha Therapy in Patients with HCV Infection Increases Plasma Phenylalanine and the Phenylalanine to Tyrosine Ratio. J Interf Cytok Res 32: 216-220.
28. Van Gool AR, Van Oijk HH, Kruit WHJ, Bannink M, Mulder PGH, et al. (2004) Pegylated interferon-α2b treatment in melanoma patients: influence on amino acids, 5-hydroxyindolacetic acid and pterine plasma concentrations. Ant-Cancer Drug 15: 587-591.
29. Nathan CF, Murray HW, Wiebe ME, Rubin BY, (1983) Identification of interferon-γ as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med 158: 670-689.
30. Murr C, Widner B, Wirleitner B, Fuchs D, (2002) Neopterin as a Marker for Immune System Activation. Curr Drug Metab 3: 175-187. Anticancer Res 19: 1721-1728.
31. Ribas GS, Sitta A, Wajner M, Vargas CR, (2011) Oxidative Stress in Phenylketonuria: What is the Evidence? Cell Mol Neurobiol 31: 653-662.
32. Hoffmann G, Wirleitner B, Fuchs D, (2003) Potential Role of Immune System Activation-Associated Production of Neopterin Derivatives in Humans. Inflamm Res 52: 313-321.
33. Witko-Sarsat V, Friedlander M, Capeillere-Blandin C, Nguyen-Khoa T, Nguyen NT, et al. (1996) Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int 49: 1304-1313.
34. Murr C, Fuith LC, Widner B, Wirleitner B, Baier-Bitterlich G, et al. (1999) Increased neopterin concentrations in patients with cancer: Indicator of oxidative stress?.
35. Parniak MA, Kaufman S, (1981) Rat Liver Phenylalanine Hydroxylase. J Biol Chem 256: 6876-6882.
36. Koizumi S, Suzuki T, Takahashi S, Satake K, Takeuchi T, et al. (1987) Sulfhydryl Modification and Activation of Phenylalanine Hydroxylase by Dinitrophenyl Alkyl Disulfide. Biochemistry 26: 6461-6465.
37. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, et al. (2000) The Protein Data Bank. Nucleic Acids Res 28: 235-242.
38. Kirchmair J, Patrick M, Distinto S, Schuster D, Spitzer GM, et al. (2008) The Protein Data Bank (PDB), Its Related Services and Software Tools as Key Components for in Silico Drug Discovery. J Med Chem 51: 7021-7040.
39. Eisensmith RC, Martinez DR, Kuzmin AI, Goltsov AA, Brown A, et al. (1996) Molecular Basis of Phenylketonuria and a Correlation Between Genotype and Phenotype in a Heterogeneous Southeastern US Population. Pediatrics 97: 512-516.
40. Guldberg P, Rey F, Zschocke J, Romano V, Francois B, et al. (1998) European Multicenter Study of Phenylalanine Hydroxylase Deficiency: Classification of 105 Mutations and a General System for Genotype-Based Prediction of Metabolic Phenotype. Am J Hum Genet 63: 71-79.
41. Erlandsen H, Patch MG, Gamez A, Straub M, Stevens RC, (2003) Structural Studies on Phenylalanine Hydroxylase and Implications Toward Understanding and Treating Phenylketonuria. Pediatrics 112: 1557-1565.
42. Andersen OA, Flatmark T, Hough E, (2001) High Resolution Crystal Structure of the Catalytic Domain of Human Phenylalanine Hydroxylase in its Catalytically Active Fe(II) Form and Binary Complex with Tetrahydrobiopterin. J Mol Biol 314: 279-291.
43. Erlandsen H, Pey AL, Gamez A, Perez B, Desviat LR, et al. (2004) Correction of kinetic and stability defects by tetrahydrobiopterin in phenylketonuria patients with certain phenylalanine hydroxylase mutations. Proc Natl Acad Sci USA 101: 16903-16908.
44. Erlandsen H, Kim JY, Patch MG, Han A, Volner A, et al. (2002) Structural Comparison of Bacterial and Human Iron-dependent Phenylalanine Hydroxylases: Similar Fold, Different Stability and Reaction Rates. J Mol Biol 320: 645-661.
45. Case DA, Darden TA, Cheatham TE III, Simmerling CL, Wang J, et al. (2008) AMBER 10. University of California, San Francisco.
46. Hornak V, Abel R, Okur A, Strockbine B, Roitberg A, et al. (2006) Comparison of Multiple Amber Force Fields and Development of Improved Protein Backbone Parameters. Proteins 65: 712-725.
47. Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA, (2004) Development and Testing of a General Amber Force Field. J Comput Chem 25: 1157-1174.
48. Bayly CI, Cieplak P, Cornell WD, Kollman PA, (1993) A Well-Behaved Electrostatic Potential Based Method Using Charge Restraints for Deriving Atomic Charges: The RESP Model. J Phys Chem 97: 10269-10280.
49. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, et al. (2004) Gaussian 03, Revision C.02. Gaussian Inc, Wallingfort CT.
50. Darden T, York D, Pedersen L, (1993) Particle mesh Ewald: An N log(N) method for Ewald sums in large systems. J Chem Phys 98: 10089-10092.
51. Jorgensen WL, Chandrasekhar J, Madura J, Impey RW, Klein ML, (1983) Comparison of Simple Potential Functions for Simulating Liquid Water. J Chem Phys 79: 926-935.
52. Adelman SA, Doll JD, (1976) Generalized Langevin Equation Approach for Atom-Solid-Surface Scattering - General Formulation for Classical Scattering Off Harmonic Solids. J Chem Phys 64: 2375-2388.
53. Ciccotti G, Ryckaert JP, (1986) Molecular Dynamics Simulation of Rigid Molecules. Comput Phys Rep 4: 345-392.
54. Sugita Y, Okamoto Y, (1999) Replica-exchange molecular dynamics method for protein folding. Chem Phys Lett 314: 141-151.
55. Patriksson A, Van der Spoel D, (2008) A temperature predictor for parallel tempering simulations. Phys Chem Chem Phys 10: 2073-2077.
56. The PyMOL Molecular Graphics System, Version 1.5.0.4 Schrödinger, LLC.
57. Durrant JD, De Oliveira CAF, McCammon JA, (2011) POVME: An Algorithm for Measuring Binding-Pocket Volumes. J Mol Graph Model 29: 773-776.
58. Andersen OA, Flatmark T, Hough E, (2002) Crystal Structure of the Ternary Complex of the Catalytic Domain of Human Phenylalanine Hydroxylase with Tetrahydrobiopterin and 3-(2-Thienyl)-L-alanine, and its Implications for the Mechanism of Catalysis and Substrate Activation. J Mol Biol 320: 1095-1108.
59. Andersen OA, Stokka AJ, Glatmark T, Hough E, (2003) 2.0 A Resolution Crystal Structures of the Ternary Complexes of Human Phenylalanine Hydroxylase Catalytic Domain with Tetrahydrobiopterin and 3-(2-Thienyl)-L-alanine or L-Norleucine: Substrate Specificity and Molecular Motions Related to Substrate Binding. J Mol Biol 333: 747-757.
60. Fitzpatrick PF, (2012) Allosteric Regulation of Phenylalanine Hydroxylase. Arch Biochem Biophys 519: 194-201.
61. Fuchs JE, Huber RG, Wallnoefer HG, Von Grafenstein S, Spitzer GM, et al. (2011) Side Chain Oxidation Modulates Local Dynamics of Phenylalanine Hydroxylase. Pteridines 22: 31-32.
62. Fuchs JE, Huber RG, Wallnoefer HG, Von Grafenstein S, Spitzer GM, et al. (2012) Conformational Changes of Phenylalanine Hydroxylase Upon Simulated Oxidative Stress. Pteridines 23: 57-58.
63. Li J, Dangott LJ, Fitzpatrick PF, (2010) Regulation of Phenylalanine Hydroxylase: Conformational Changes Upon Phenylalanine Binding Detected by Hydrogen/Deuterium Exchange and Mass Spectrometry. Biochemistry 49: 3327-3335.
64. Sura GR, Lasagna M, Gawandi V, Reinhart GD, Fitzpatrick PF, (2006) Effects of Ligands on the Mobility of an Active-Site Loop in Tyrosine Hydroxylase as Monitored by Flourescence Anisotropy. Biochemistry 45: 9632-9638.
65. Cerreto M, Cavaliere P, Carluccio C, Amato F, Zagari A, et al. (2011) Natural phenylalanine hydroxylase variants that confer a mild phenotype affect the enzyme's conformational stability and oligomerization equilibrium. Biochim Biophys Acta 1812: 1435-1445.
66. Gersting SW, Femter KF, Staudig M, Messing DD, Danecka MK, et al. (2008) Loss of Function in Phenylketonuria Is Caused by Impaired Molecular Motions and Conformational Instability. Am J Hum Genet 83: 5-17.
67. Miranda FF, Thorolfsson M, Teigen K, Sanchez-Ruiz JM, Martinez A, (2004) Structural and stability effects of phosphorylation: Localized structural changes in phenylalanine hydroxylase. Protein Sci 13: 1219-1226.
68. Teigen K, Martinez A, (2003) Probing Cofactor Specificity in Phenylalanine Hydroxylase by Molecular Dynamics Simulations. J Biomol Struct Dyn 20: 733-740.
69. Teigen K, McKinney JA, Haavik J, Martinez A, (2007) Selectivity and Affinity Determinants for Ligand Binding to the Aromatic Amino Acid Hydroxylases. Curr Med Chem 14: 455-467.
70. Kemp M, Go YM, Jones DP, (2008) Non-equilibrium thermodynamics of thiol/disulfide redox systems: A perspective on redox systems biology. Free Radic Biol Med 44: 921-937.
71. Schroeder BO, Wu Z, Nuding S, Groscurth S, Marcinowski M, et al. (2011) Reduction of disulphide bonds unmasks potent antimicrobial activity of human β-defensin 1. Nature 469: 419-425.
72. Tanner JJ, Parsons ZD, Cummings AH, Zhou H, Gates KS, (2011) Redox Regulation of Protein Tyrosine Phosphatases: Structural and Chemical Aspects. Antioxid Redox Signaling 15: 77-97.
73. Wang MY, Ji SR, Bai CJ, El Kebir D, Li HY, et al. (2011) A redox switch in C-reactive protein modulates activation of endothelial cells. FASEB J 25: 3186-3196.