Structural Studies on Phenylalanine Hydroxylase and Implications Toward Understanding and Treating Phenylketonuria

Pediatrics

Volumn 112, Issue 6 II, 2003, Pages 1557-1565

  Erlandsen, Heidi ^a   Patch, Marianne G ^a   Gamez, Alejandra ^a   Straub, Mary ^a   Stevens, Raymond C ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

3 dimensional structure; BH4 responsive hyperphenylalaninemia; Co factor therapy; Phenylalanine hydroxylase; Phenylketonuria; Structural basis

Indexed keywords

PHENYLALANINE 4 MONOOXYGENASE; TETRAHYDROBIOPTERIN;

AMINO ACID SEQUENCE; CONFERENCE PAPER; ENZYME ACTIVE SITE; ENZYME SPECIFICITY; GENE MUTATION; HUMAN; HYPERPHENYLALANINEMIA; MISSENSE MUTATION; PHENYLKETONURIA; PRIORITY JOURNAL; X RAY CRYSTALLOGRAPHY;

AMINO ACID SEQUENCE; ANIMALS; BIOPTERIN; CRYSTALLOGRAPHY, X-RAY; GENOTYPE; HUMANS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; MUTATION, MISSENSE; PHENYLALANINE HYDROXYLASE; PHENYLKETONURIAS; POINT MUTATION; PROTEIN CONFORMATION; PROTEIN STRUCTURE, SECONDARY;

EID: 0346753973     PISSN: 00314005     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Conference Paper

References (56)

1. Erlandsen H, Fusetti F, Martinez A, Hough E, Flatmark T, Stevens RC. Crystal structure of the catalytic domain of human phenylalanine hydroxylase reveals the structural basis for phenylketonuria. Nat Struct Biol. 1997;4:995-1000
2. Fusetti F, Erlandsen H, Flatmark T, Stevens RC. Structure of tetrameric human phenylalanine hydroxylase and its implications for phenylketonuria. J Biol Chem. 1998;273:16962-16967
3. Kobe B, Jennings IG, House CM, et al. Structural basis of autoregulation of phenylalanine hydroxylase. Nat Struct Biol. 1999;6:442-448
4. Erlandsen H, Bjørgo E, Flatmark T, Stevens RC. Crystal structure and site-specific mutagenesis of pterin-bound human phenylalanine hydroxylase. Biochemistry. 2000;39:2208-2217
5. Andersen OA, Flatmark T, Hough E. 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. 2001;314:279-291
6. Andersen OA, Flatmark T, Hough E. 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. 2002;320:1095-1108
7. Martinez A, Knappskog PM, Olafdottir S, et al. Expression of recombinant human phenylalanine hydroxylase as fusion protein in Escherichia coli circumvents proteolytic degradation by host cell proteases. Biochem J. 1995;306:589-597
8. Erlandsen H, Stevens RC. The structural basis of phenylketonuria. Mol Genet Metab. 1999;68:103-125
9. Goodwill KE, Sabatier C, Marks C, Raag R, Fitzpatrick PF, Stevens RC. Crystal structure of tyrosine hydroxylase at 2.3 Å and its implications for inherited neurodegenerative diseases. Nat Struct Biol. 1997;4: 578-585
10. Knappskog PM, Flatmark T, Aarden JM, Haavik J, Martinez A. Structure/function relationships in human phenylalanine hydroxylase. Effect of terminal deletions on the oligomerization, activation and cooperativity of substrate binding to the enzyme. Eur J Biochem. 1996;242:813-821
11. Martinez A, Andersson KK, Haavik J, Flatmark T. EPR and 1H-NMR spectroscopic studies on the paramagnetic iron at the active site of phenylalanine hydroxylase and its interaction with substrates and inhibitors. Eur J Biochem. 1991;198:675-682
12. Gibbs BS, Wojchowski D, Benkovic SJ. Expression of rat liver phenylalanine hydroxylase in insect cells and site-directed mutagenesis of putative non-heme iron-binding sites. J Biol Chem. 1993;268:8046-8052
13. Kappock TJ, Caradonna JP. Pterin-dependent amino acid hydroxylases. Chem Rev. 1996;96:2659-2756
14. Hufton SE, Jennings IG, Cotton RGH. Structure and function of the aromatic amino acid hydroxylases. Biochem J. 1995;311:353-366
15. Jennings IG, Kemp BE, Cotton RGH. Localization of cofactor binding sites with monoclonal anti-idiotype antibodies: phenylalanine hydroxylase. Proc Natl Acad Sci U S A. 1991;88:5734-5738
16. Flatmark T, Stevens RC. Structural insights into the aromatic amino acid hydroxylases and their disease-related mutant forms. Chem Rev. 1999;99:2137-2160
17. Xia, T, Gray DW, Shiman R. Regulation of rat liver phenylalanine hydroxylase. III. Control of catalysis by (6R)-tetrahydrobiopterin and phenylalanine. J Biol Chem. 1994;269:24657-24665
18. Døskeland AP, Døskeland SO, Øgreid D, Flatmark T. The effect of ligands of phenylalanine 4-monooxygenase on the cAMP-dependent phosphorylation of the enzyme. J Biol Chem. 1984;259:11242-11248
19. Gamez A, Perez B, Ugarte M, Desviat LR. Expression analysis of phenylketonuria mutations. Effect on folding and stability of the phenylalanine hydroxylase protein. J Biol Chem. 2000;275:29737-4220
20. Kayaalp E, Treacy E, Waters PJ, Byck S, Nowacki P, Scriver CR. Human phenylalanine hydroxylase mutations and hyperphenylalaninemia phenotypes: a metanalysis of genotype-phenotype correlations. Am J Hum Genet. 1997;61:1309-1317
21. Flatmark T, Knappskog PM, Bjørgo E, Martinez A. Molecular characterization of disease related mutant forms of human phenylalanine hydroxylase and tyrosine hydroxylase. In: Pfleiderer W, Rokos H, eds. Chemistry and Biology of Pteridines and Folates. London, UK: Blackwell Science; 1997:503-508
22. Knappskog PM, Eiken HG, Martinez A, Bruland O, Apold J, Flatmark T. PKU mutation (D143G) associated with an apparent high residual enzyme activity: expression of a kinetic variant form of phenylalanine hydroxylase in three different systems. Hum Mutat. 1996;8:236-246
23. Guldberg P, Romano V, Ceratto N, et al. Mutational spectrum of phenylalanine hydroxylase deficiency in Sicily: implications for diagnosis of hyperphenylalaninemia in southern Europe. Hum Mol Genet. 1993;2:1703-1707
24. Takahashi K, Masamune A, Kure S, Matsubara Y, Narisawa K. Ectopic transcription: an application to the analysis of splicing errors in phenylalanine hydroxylase mRNA. Acta Paediatr Suppl. 1994;407:45-46
25. Bjørgo E, Knappskog PM, Martinez A, Stevens RC, Flatmark T. Partial characterization and three-dimensional-structural localization of eight mutations in exon 7 of the human phenylalanine hydroxylase gene associated with phenylketonuria. Eur J Biochem. 1998;257:1-10
26. Okano Y, Eisensmith RC, Guttler F, et al. Molecular basis of phenotypic heterogeneity in phenylketonuria. N Engl J Med. 1991;324:1232-1238
27. Knappskog PM, Olafsdottir S, Haavik J, et al. Expression of wildtype and mutant forms of human phenylalanine hydroxylase in E. coli. In: Ayling JE, Gopal Nair M, Baugh CM, eds. Chemistry and Biology of Pteridines and Folates. New York, NY: Plenum Press; 1993:59-62
28. Okano Y, Wang T, Eisensmith RC, Steinmann B, Gitzelmann R, Woo SL. Missense mutations associated with RFLP haplotypes 1 and 4 of the human phenylalanine hydroxylase gene. Am J Hum Genet. 1990;46:18-25
29. Baric I, Mardesic D, Sarnavoka V, Lichter-Konecki U, Konecki DS, Trefz FK. Geographical distribution of the P281L mutation at the phenylalanine hydroxylase locus: possible origin in southeastern Europe. J Inherit Metab Dis. 1994;7:376-377
30. Dworniczak B, Grudda K, Stumper J, Bartholome K, Aulehla-Scholz C, Horst J. Phenylalanine hydroxylase gene: novel missense mutation in exon 7 causing severe phenylketonuria. Genomics. 1991;9:193-199
31. Okano Y, Wang T, Eisensmith RC, et al. Phenylketonuria missense mutations in the Mediterranean. Genomics. 1991;9:96-103
32. McKinney J, Teigen K, Frøystein NA, et al. Conformation of the substrate and pterin cofactor bound to human tryptophan hydroxylase. Important role of Phe313 in substrate specificity. Biochemistry. 2001;40: 15591-15601
33. Benit P, Rey F, Melle D, Munnich A, Rey J. Five novel missense mutations of the phenylalanine hydroxylase gene in phenylketonuria. Hum Mutat. 1994;4:229-231
34. Guldberg P, Levy HL, Hanley WB, et al. Phenylalanine hydroxylase gene mutations in the United States: report from the Maternal PKU Collaborative Study. Am J Hum Genet. 1996;59:84-94
35. Knappskog PM, Eiken HG, Martinez A, Flatmark T, Apold J. The PKU mutation S349P causes complete loss of catalytic activity in the recombinant phenylalanine hydroxylase enzyme. Hum Genet. 1995;95:171-173
36. De Lucca M, Perez B, Desviat LR, Ugarte M. Molecular basis of phenylketonuria in Venezuela: presence of two novel null mutations. Hum Mutat. 1998;11:354-359
37. Eiken HG, Knappskog PM, Boman H, et al. Relative frequency, heterogeneity and geographic clustering of PKU mutations in Norway. Eur J Hum Genet. 1996;4:205-213
38. John SW, Scriver CR, Laframboise R, Rozen R. In vitro and in vivo correlations for I65T and M1V mutations at the phenylalanine hydroxylase locus. Hum Mutat. 1992;1:147-153
39. Waters PJ, Parniak MA, Hewson AS, Scriver CR. Alterations in protein aggregation and degradation due to mild and severe missense mutations (A104D, R157N) in the human phenylalanine hydroxylase gene (PAH). Hum Mutat. 1998;12:344-354
40. Wang T, Okano Y, Eisensmith RC, et al. Missense mutations prevalent in Orientals with phenylketonuria: molecular characterization and clinical implications. Genomics. 1991;10:449-456
41. DiLella AG, Marvit J, Brayton K, Woo SL. An amino-acid substitution involved in phenylketonuria is in linkage disequilibrium with DNA haplotype 2. Nature. 1987;327:333-336
42. Svensson E, Eisensmith RC, Dworniczak B, et al. Two missense mutations causing mild hyperphenylalaninemia associated with DNA haplotype 12. Hum Mutat. 1992;1:129-137
43. Perez B, Desviat LR, De Lucca M, Ugarte M. Spectrum and origin of phenylketonuria mutations in Spain. Acta Paediatr Suppl. 1994;407:34-36
44. Mallolas J, Campistol J, Lambruschini N, et al. Two novel mutations in exon 11 of the PAH gene (V1163del TG and P362T) associated with classic phenylketonuria and mild phenylketonuria. Hum Mutat. 1998;11:482
45. Guldberg P, Henriksen KF, Guttler F. Molecular analysis of phenylketonuria in Denmark: 99% of the mutations detected by denaturing gradient gel electrophoresis. Genomics. 1993;17:141-146
46. Walter JH, White FJ, Hall SK, et al. How practical are recommendations for dietary control in phenylketonuria? Lancet. 2002;360:55-57
47. Levy HL. Phenylketonuria: old disease, new approach to treatment. Proc Natl Acad Sci U S A. 1999;96:1811-1813
48. Sarkissian CN, Shao Z, Blain F, et al. A different approach to treatment of phenylketonuria: phenylalanine degradation with recombinant phenylalanine ammonia lyase. Proc Natl Acad Sci U S A. 1999;96:2339-2344
49. 4 responsiveness in patients with mild forms of hyperphenylalaninaemia and phenylketonuria. J Inherit Metab Dis. 2001;24:213-230
50. Lassker U, Zschocke J, Blau N, Santer R. Tetrahydrobiopterin responsiveness in phenylketonuria. Two new cases and a review of molecular genetic findings. J Inherit Metab Dis. 2002;25:65-70
51. Blau N, Trefz FK. Tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency: possible regulation of gene expression in a patient with the homozygous L48S mutation. Mol Genet Metab. 2002;75:186-187
52. Kure S, Hou DC, Ohura T, et al. Tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency. J Pediatr. 1999;135:375-378
53. 4). J Inherit Metab Dis. 2000;23(suppl 1):47
54. Spaapen LJM, Bakker JA, Velter C, et al. Tetrahydrobiopterin-responsive hyperphenylalaninemia (HPA) in Dutch neonates. J Inherit Metab Dis. 2000;23(suppl 1):45
55. Ames BN, Elson-Schwab I, Silver EA. High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased K(m)): relevance to genetic disease and polymorphisms. Am J Clin Nutr. 2002;75:616-658
56. Kabsch W, Sander C. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers. 1983;22:2577-2637