Pahenu1 is a mouse model for tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency and promotes analysis of the pharmacological chaperone mechanism in vivo

Human Molecular Genetics

Volumn 19, Issue 10, 2010, Pages 2039-2049

  Gersting, Søren W ^a   Lagler, Florian B ^b   Eichinger, Anna ^a   Kemter, Kristina F ^a   Danecka, Marta K ^a   Messing, Dunja D ^a   Staudigl, Michael ^a   Domdey, Katharina A ^a   Zsifkovits, Clemens ^b   Fingerhut, Ralph ^c,d   Glossmann, Hartmut ^b   Roscher, Adelbert A ^a   Muntau, Ania C ^a  

^a LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^b INNSBRUCK MEDICAL UNIVERSITY   (Austria)

^c Labor Becker   (Germany)

^d UNIVERSITY CHILDREN S HOSPITAL   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

PHENYLALANINE 4 MONOOXYGENASE; SAPROPTERIN; 5,6,7,8-TETRAHYDROBIOPTERIN; BIOPTERIN; CHAPERONE; DRUG DERIVATIVE; PHENYLALANINE; TETRAHYDROBIOPTERIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DRUG MECHANISM; ENZYME ACTIVITY; IMMUNOBLOTTING; IN VITRO STUDY; IN VIVO STUDY; LIGHT SCATTERING; MOUSE; NONHUMAN; OLIGOMERIZATION; PHENOTYPE; PHENYLKETONURIA; PLASMID; POLYACRYLAMIDE GEL ELECTROPHORESIS; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN CONFORMATION; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FOLDING; PROTEIN PURIFICATION; SITE DIRECTED MUTAGENESIS; TREATMENT RESPONSE; AMINO ACID SUBSTITUTION; ANIMAL; CELL STRAIN COS1; CERCOPITHECUS; CHEMISTRY; DISEASE MODEL; DRUG EFFECT; GENETICS; HUMAN; HYDROXYLATION; KINETICS; METABOLISM; MUTATION; PROTEIN PROCESSING; PROTEIN QUATERNARY STRUCTURE;

AMINO ACID SUBSTITUTION; ANIMALS; BIOPTERIN; CERCOPITHECUS AETHIOPS; COS CELLS; DISEASE MODELS, ANIMAL; HUMANS; HYDROXYLATION; KINETICS; MICE; MOLECULAR CHAPERONES; MUTATION; PHENYLALANINE; PHENYLALANINE HYDROXYLASE; PROTEIN FOLDING; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEIN STRUCTURE, QUATERNARY;

EID: 77952483396     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddq085     Document Type: Article

References (41)

1. Selkoe, D.J. (2004) Cell biology of protein misfolding: the examples of Alzheimer's and Parkinson's diseases. Nat. Cell Biol., 6, 1054-1061.
2. Soto, C. (2003) Unfolding the role of protein misfolding in neurodegenerative diseases. Nat. Rev. Neurosci., 4, 49-60.
3. Winklhofer, K.F., Tatzelt, J. and Haass, C. (2008) The two faces of protein misfolding: gain-and loss-of-function in neurodegenerative diseases. EMBO J., 27, 336-349.
4. Gersting, S.W., Kemter, K.F., Staudigl, M., Messing, D.D., Danecka, M.K., Lagler, F.B., Sommerhoff, C.P., Roscher, A.A. and Muntau, A.C. (2008) Loss of function in phenylketonuria is caused by impaired molecular motions and conformational instability. Am. J. Hum. Genet., 83, 5-17.
5. Conn, P.M., Ulloa-Aguirre, A., Ito, J. and Janovick, J.A. (2007) G protein-coupled receptor trafficking in health and disease: lessons learned to prepare for therapeutic mutant rescue in vivo. Pharmacol. Rev., 59, 225-250.
6. Balch, W.E., Morimoto, R.I., Dillin, A. and Kelly, J.W. (2008) Adapting proteostasis for disease intervention. Science, 319, 916-919.
7. Mu, T.W., Ong, D.S., Wang, Y.J., Balch, W.E., Yates, J.R. 3rd, Segatori, L. and Kelly, J.W. (2008) Chemical and biological approaches synergize to ameliorate protein-folding diseases. Cell, 134, 769-781.
8. Gregersen, N., Bross, P., Vang, S. and Christensen, J.H. (2006) Protein misfolding and human disease. Annu. Rev. Genomics Hum. Genet., 7, 103-124.
9. Cohen, F.E. and Kelly, J.W. (2003) Therapeutic approaches to protein-misfolding diseases. Nature, 426, 905-909.
10. Conn, P.M. and Janovick, J.A. (2009) Drug development and the cellular quality control system. Trends Pharmacol. Sci., 30, 228-233.
11. Powers, E.T., Morimoto, R.I., Dillin, A., Kelly, J.W. and Balch, W.E. (2009) Biological and chemical approaches to diseases of proteostasis deficiency. Annu. Rev. Biochem., 78, 959-991.
12. Muntau, A.C., Röschinger, W., Habich, M., Demmelmair, H., Hoffmann, B., Sommerhoff, C.P. and Roscher, A.A. (2002) Tetrahydrobiopterin as an alternative treatment for mild phenylketonuria. N. Engl. J. Med., 347, 2122-2132.
13. Aguado, C., Perez, B., Ugarte, M. and Desviat, L.R. (2006) Analysis of the effect of tetrahydrobiopterin on PAH gene expression in hepatoma cells. FEBS Lett., 580, 1697-1701.
14. Erlandsen, H., Pey, A.L., Gamez, A., Perez, B., Desviat, L.R., Aguado, C., Koch, R., Surendran, S., Tyring, S., Matalon, R. 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.
15. 4-responsive patients. Mol. Genet. Metab., 86 (Suppl. 1), S11-S16.
16. Pey, A.L., Perez, B., Desviat, L.R., Martinez, M.A., Aguado, C., Erlandsen, H., Gamez, A., Stevens, R.C., Thorolfsson, M., Ugarte, M. et al. (2004) Mechanisms underlying responsiveness to tetrahydrobiopterin in mild phenylketonuria mutations. Hum. Mutat., 24, 388-399.
17. Kure, S., Sato, K., Fujii, K., Aoki, Y., Suzuki, Y., Kato, S. and Matsubara, Y. (2004) Wild-type phenylalanine hydroxylase activity is enhanced by tetrahydrobiopterin supplementation in vivo: an implication for therapeutic basis of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency. Mol. Genet. Metab., 83, 150-156.
18. Scavelli, R., Ding, Z., Blau, N., Haavik, J., Martinez, A. and Thony, B. (2005) Stimulation of hepatic phenylalanine hydroxylase activity but not Pah-mRNA expression upon oral loading of tetrahydrobiopterin in normal mice. Mol. Genet. Metab., 86 (Suppl. 1), S153-S155.
19. Thöny, B., Ding, Z. and Martinez, A. (2004) Tetrahydrobiopterin protects phenylalanine hydroxylase activity in vivo: implications for tetrahydrobiopterin-responsive hyperphenylalaninemia. FEBS Lett., 577, 507-511.
20. McDonald, J.D. and Charlton, C.K. (1997) Characterization of mutations at the mouse phenylalanine hydroxylase locus. Genomics, 39, 402-405.
21. McDonald, J.D., Bode, V.C., Dove, W.F. and Shedlovsky, A. (1990) Pahhph-5: a mouse mutant deficient in phenylalanine hydroxylase. Proc. Natl Acad. Sci. USA, 87, 1965-1967.
22. Sarkissian, C.N., Boulais, D.M., McDonald, J.D. and Scriver, C.R. (2000) A heteroallelic mutant mouse model: a new orthologue for human hyperphenylalaninemia. Mol. Genet. Metab., 69, 188-194.
23. Shedlovsky, A., McDonald, J.D., Symula, D. and Dove, W.F. (1993) Mouse models of human phenylketonuria. Genetics, 134, 1205-1210.
24. McDonald, J.D., Andriolo, M., Cali, F., Mirisola, M., Puglisi-Allegra, S., Romano, V., Sarkissian, C.N. and Smith, C.B. (2002) The phenylketonuria mouse model: a meeting review. Mol. Genet. Metab., 76, 256-261.
25. Ledley, F.D., Grenett, H.E., Dunbar, B.S. and Woo, S.L. (1990) Mouse phenylalanine hydroxylase. Homology and divergence from human phenylalanine hydroxylase. Biochem. J., 267, 399-405.
26. Treacy, E.P., Delente, J.J., Elkas, G., Carter, K., Lambert, M., Waters, P.J. and Scriver, C.R. (1997) Analysis of phenylalanine hydroxylase genotypes and hyperphenylalaninemia phenotypes using l-[1-13C]phenylalanine oxidation rates in vivo: a pilot study. Pediatr. Res., 42, 430-435.
27. Martinez, A., Knappskog, P.M., Olafsdottir, S., Doskeland, A.P., Eiken, H.G., Svebak, R.M., Bozzini, M., Apold, J. and Flatmark, T. (1995) Expression of recombinant human phenylalanine hydroxylase as fusion protein in Escherichia coli circumvents proteolytic degradation by host cell proteases. Isolation and characterization of the wild-type enzyme. Biochem. J., 306 (Pt 2), 589-597.
28. Kappock, T.J., Harkins, P.C., Friedenberg, S. and Caradonna, J.P. (1995) Spectroscopic and kinetic properties of unphosphorylated rat hepatic phenylalanine hydroxylase expressed in Escherichia coli. Comparison of resting and activated states. J. Biol. Chem., 270, 30532-30544.
29. Thorolfsson, M., Ibarra-Molero, B., Fojan, P., Petersen, S.B., Sanchez-Ruiz, J.M. and Martinez, A. (2002) l-phenylalanine binding and domain organization in human phenylalanine hydroxylase: a differential scanning calorimetry study. Biochemistry (Mosc.), 41, 7573-7585.
30. Maier, E.M., Gersting, S.W., Kemter, K.F., Jank, J.M., Reindl, M., Messing, D.D., Truger, M.S., Sommerhoff, C.P. and Muntau, A.C. (2009) Protein misfolding is the molecular mechanism underlying MCADD identified in newborn screening. Hum. Mol. Genet., 18, 1612-1623.
31. Fontana, A., de Laureto, P.P., Spolaore, B., Frare, E., Picotti, P. and Zambonin, M. (2004) Probing protein structure by limited proteolysis. Acta Biochim. Pol., 51, 299-321.
32. Mitnaul, L.J. and Shiman, R. (1995) Coordinate regulation of tetrahydrobiopterin turnover and phenylalanine hydroxylase activity in rat liver cells. Proc. Natl Acad. Sci. USA, 92, 885-889.
33. Xia, T., Gray, D.W. and Shiman, R. (1994) Regulation of rat liver phenylalanine hydroxylase. III. Control of catalysis by (6R)-tetrahydrobiopterin and phenylalanine. J. Biol. Chem., 269, 24657-24665.
34. Shiman, R. and Gray, D.W. (1980) Substrate activation of phenylalanine hydroxylase. A kinetic characterization. J. Biol. Chem., 255, 4793-4800.
35. Stokka, A.J., Carvalho, R.N., Barroso, J.F. and Flatmark, T. (2004) Probing the role of crystallographically defined/predicted hinge-bending regions in the substrate-induced global conformational transition and catalytic activation of human phenylalanine hydroxylase by single-site mutagenesis. J. Biol. Chem., 279, 26571-26580.
36. Stokka, A.J. and Flatmark, T. (2003) Substrate-induced conformational transition in human phenylalanine hydroxylase as studied by surface plasmon resonance analyses: the effect of terminal deletions, substrate analogues and phosphorylation. Biochem. J., 369, 509-518.
37. Andersen, O.A., Flatmark, T. and Hough, E. (2001) High resolution crystal structures 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.
38. Teigen, K. and Martinez, A. (2003) Probing cofactor specificity in phenylalanine hydroxylase by molecular dynamics simulations. J. Biomol. Struct. Dyn., 20, 733-740.
39. Kaufman, S. (1993) The phenylalanine hydroxylating system. Adv. Enzymol. Relat. Areas Mol. Biol., 67, 77-264.
40. Pey, A.L., Ying, M., Cremades, N., Velazquez-Campoy, A., Scherer, T., Thöny, B., Sancho, J. and Martinez, A. (2008) Identification of pharmacological chaperones as potential therapeutic agents to treat phenylketonuria. J. Clin. Invest., 118, 2858-2867.
41. Miranda, F.F., Teigen, K., Thorolfsson, M., Svebak, R.M., Knappskog, P.M., Flatmark, T. and Martinez, A. (2002) Phosphorylation and mutations of Ser(16) in human phenylalanine hydroxylase. Kinetic and structural effects. J. Biol. Chem., 277, 40937-40943.