DB code: D00496

CATH domain 3.30.70.260 : Alpha-Beta Plaits
1.10.800.10 : Phenylalanine Hydroxylase Catalytic domain
E.C. 1.14.16.1
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.30.70.260 : Alpha-Beta Plaits T00247
1.10.800.10 : Phenylalanine Hydroxylase D00478

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam RefSeq
P04176 Phenylalanine-4-hydroxylase
PAH
EC 1.14.16.1
Phe-4-monooxygenase
PF01842 (ACT)
PF00351 (Biopterin_H)
[Graphical View]
P00439 Phenylalanine-4-hydroxylase
PAH
EC 1.14.16.1
Phe-4-monooxygenase
PF01842 (ACT)
PF00351 (Biopterin_H)
[Graphical View]
NP_000268.1 (Protein)
NM_000277.1 (DNA/RNA sequence)

KEGG enzyme name
phenylalanine 4-monooxygenase
phenylalaninase
phenylalanine 4-hydroxylase
phenylalanine hydroxylase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P00439 PH4H_HUMAN L-phenylalanine + tetrahydrobiopterin + O(2) = L-tyrosine + 4a-hydroxytetrahydrobiopterin. Homodimer. Fe(2+) ion.
P04176 PH4H_RAT L-phenylalanine + tetrahydrobiopterin + O(2) = L-tyrosine + 4a-hydroxytetrahydrobiopterin. Homodimer. Fe(2+) ion.

KEGG Pathways
Map code Pathways E.C.
MAP00400 Phenylalanine, tyrosine and tryptophan biosynthesis

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00023 C00079 C00272 C00007 C00082 C15522
E.C.
Compound Iron L-Phenylalanine Tetrahydrobiopterin O2 L-Tyrosine 4a-hydroxytetrahydrobiopterin
Type heavy metal amino acids,aromatic ring (only carbon atom) amide group,amine group,aromatic ring (with nitrogen atoms),carbohydrate others amino acids,aromatic ring (only carbon atom) amine group,aromatic ring (with nitrogen atoms),carbohydrate
ChEBI 18248
82664
17295
58095
59560
15379
26689
27140
17895
58315
PubChem 23925
6140
6925665
44257
977
6057
6942100
46173804
1phzA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
2phmA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1dmwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_FE Unbound Analogue:HBI Unbound Unbound Unbound
1j8tA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FE2 Unbound Unbound Unbound Unbound Unbound
1j8uA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FE2 Unbound Bound:H4B Unbound Unbound Unbound
1kw0A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FE2 Analogue:TIH Bound:H4B Analogue:HOH_435 Unbound Unbound
1lrmA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_FE Unbound Analogue:HBI Unbound Unbound Unbound
1mmkA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FE2 Analogue:TIH Bound:H4B Unbound Unbound Unbound
1mmtA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FE2 Analogue:NLE Bound:H4B Analogue:HOH_575 Unbound Unbound
1pahA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_FE Unbound Unbound Unbound Unbound Unbound
1tdwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_FE Unbound Unbound Unbound Unbound Unbound
1tg2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_FE Unbound Analogue:H2B Unbound Unbound Unbound
2pahA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_FE Unbound Unbound Unbound Unbound Unbound
2pahB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_FE Unbound Unbound Unbound Unbound Unbound
3pahA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_FE Unbound Unbound Unbound Analogue:ALE Unbound
4pahA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_FE Unbound Unbound Unbound Analogue:LNR Unbound
5pahA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_FE Unbound Unbound Unbound Analogue:LDP Unbound
6pahA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_FE Unbound Unbound Unbound Analogue:DAH Unbound
1phzA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_FE Unbound Unbound Unbound Unbound Unbound
2phmA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_FE Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
PDB;1pah & Swiss-prot;P00439, P04176

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1phzA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain (phospholylation) invisible S16 (phosphorylation site)
2phmA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain (phospholylation) invisible S16 (phosphorylation site)
1dmwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 285;HIS 290;GLU 330(Iron binding)
1j8tA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 285;HIS 290;GLU 330(Iron binding)
1j8uA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 285;HIS 290;GLU 330(Iron binding)
1kw0A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 285;HIS 290;GLU 330(Iron binding)
1lrmA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 285;HIS 290;GLU 330(Iron binding)
1mmkA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 285;HIS 290;GLU 330(Iron binding)
1mmtA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 285;HIS 290;GLU 330(Iron binding)
1pahA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 285;HIS 290;GLU 330(Iron binding)
1tdwA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 285;HIS 290;GLU 330(Iron binding)
1tg2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 285;HIS 290;GLU 330(Iron binding)
2pahA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 285;HIS 290;GLU 330(Iron binding)
2pahB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 285;HIS 290;GLU 330(Iron binding)
3pahA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 285;HIS 290;GLU 330(Iron binding)
4pahA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 285;HIS 290;GLU 330(Iron binding)
5pahA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 285;HIS 290;GLU 330(Iron binding)
6pahA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 285;HIS 290;GLU 330(Iron binding)
1phzA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 285;HIS 290;GLU 330(Iron binding)
2phmA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 285;HIS 290;GLU 330(Iron binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[15]
p.997-998
[25]
p.817-819
[26]
p.444-445
[29]
Scheme 1, Fig.5, p.2211-2216
[38]
p.287-288
[43]
Fig.8, p.1103-1104
[47]
p.1071-1073, Fig.6

References
[1]
Resource
Comments
Medline ID
PubMed ID 4087300
Journal J Mol Biol
Year 1985
Volume 186
Pages 479-80
Authors Guddat LW, Cowan SW, Machin KJ, Isaacs NW, Cotton RG
Title Crystallization and preliminary crystallographic data of the Fab fragment of an anti-phenylalanine hydroxylase monoclonal antibody.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 3769914
Journal Eur J Biochem
Year 1986
Volume 160
Pages 1-8
Authors Haavik J, Doskeland AP, Flatmark T
Title Stereoselective effects in the interactions of pterin cofactors with rat-liver phenylalanine 4-monooxygenase.
Related PDB
Related UniProtKB
[3]
Resource
Comments REVIEW ON PKU VARIANTS
Medline ID 91061429
PubMed ID 2246858
Journal J Inherit Metab Dis
Year 1990
Volume 13
Pages 739-50
Authors Cotton RG
Title Heterogeneity of phenylketonuria at the clinical, protein and DNA levels.
Related PDB
Related UniProtKB P00439
[4]
Resource
Comments
Medline ID
PubMed ID 1681899
Journal Biochemistry
Year 1991
Volume 30
Pages 10226-35
Authors Bailey SW, Dillard SB, Ayling JE
Title Role of C6 chirality of tetrahydropterin cofactor in catalysis and regulation of tyrosine and phenylalanine hydroxylases.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 1646718
Journal Eur J Biochem
Year 1991
Volume 198
Pages 675-82
Authors Martinez A, Andersson KK, Haavik J, Flatmark T
Title EPR and 1H-NMR spectroscopic studies on the paramagnetic iron at the active site of phenylalanine hydroxylase and its interaction with substrates and inhibitors.
Related PDB
Related UniProtKB
[6]
Resource
Comments REVIEW ON PKU VARIANTS
Medline ID 91348681
PubMed ID 1679029
Journal Hum Genet
Year 1991
Volume 87
Pages 377-88
Authors Konecki DS, Lichter-Konecki U
Title The phenylketonuria locus: current knowledge about alleles and mutations of the phenylalanine hydroxylase gene in various populations.
Related PDB
Related UniProtKB P00439
[7]
Resource
Comments
Medline ID
PubMed ID 2016740
Journal J Mol Biol
Year 1991
Volume 218
Pages 495-8
Authors Celikel R, Davis MD, Dai XP, Kaufman S, Xuong NH
Title Crystallization and preliminary X-ray analysis of phenylalanine hydroxylase from rat liver.
Related PDB
Related UniProtKB
[8]
Resource
Comments REVIEW ON PKU VARIANTS
Medline ID 93244826
PubMed ID 1301187
Journal Hum Mutat
Year 1992
Volume 1
Pages 13-23
Authors Eisensmith RC, Woo SL
Title Molecular basis of phenylketonuria and related hyperphenylalaninemias: mutations and polymorphisms in the human phenylalanine hydroxylase gene.
Related PDB
Related UniProtKB P00439
[9]
Resource
Comments
Medline ID
PubMed ID 8031788
Journal Biochemistry
Year 1994
Volume 33
Pages 8532-7
Authors Balasubramanian S, Carr RT, Bender CJ, Peisach J, Benkovic SJ
Title Identification of metal ligands in Cu(II)-inhibited Chromobacterium violaceum phenylalanine hydroxylase by electron spin echo envelope modulation analysis of histidine to serine mutations.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 7914195
Journal J Biol Chem
Year 1994
Volume 269
Pages 20369-75
Authors Dickson PW, Jennings IG, Cotton RG
Title Delineation of the catalytic core of phenylalanine hydroxylase and identification of glutamate 286 as a critical residue for pterin function.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 8573072
Journal Biochem J
Year 1996
Volume 313
Pages 409-14
Authors Doskeland AP, Martinez A, Knappskog PM, Flatmark T
Title Phosphorylation of recombinant human phenylalanine hydroxylase: effect on catalytic activity, substrate activation and protection against non-specific cleavage of the fusion protein by restriction protease.
Related PDB
Related UniProtKB
[12]
Resource
Comments CHARACTERIZATION OF VARIANT PKU GLY-143
Medline ID 9704451
PubMed ID 8889583
Journal Hum Mutat
Year 1996
Volume 8
Pages 236-46
Authors Knappskog PM, Eiken HG, Martinez A, Bruland O, Apold J, Flatmark T
Title PKU mutation (D143G) associated with an apparent high residual enzyme activity: expression of a kinetic variant form of phenylalanine hydroxylase in three different systems.
Related PDB
Related UniProtKB P00439
[13]
Resource
Comments
Medline ID
PubMed ID 9434741
Journal Arch Biochem Biophys
Year 1997
Volume 348
Pages 295-302
Authors Daubner SC, Hillas PJ, Fitzpatrick PF
Title Expression and characterization of the catalytic domain of human phenylalanine hydroxylase.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 9109411
Journal FEBS Lett
Year 1997
Volume 406
Pages 171-4
Authors Erlandsen H, Martinez A, Knappskog PM, Haavik J, Hough E, Flatmark T
Title Crystallization and preliminary diffraction analysis of a truncated homodimer of human phenylalanine hydroxylase.
Related PDB
Related UniProtKB
[15]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 117-424
Medline ID 98069646
PubMed ID 9406548
Journal Nat Struct Biol
Year 1997
Volume 4
Pages 995-1000
Authors Erlandsen H, Fusetti F, Martinez A, Hough E, Flatmark T, Stevens RC
Title Crystal structure of the catalytic domain of human phenylalanine hydroxylase reveals the structural basis for phenylketonuria.
Related PDB 1pah
Related UniProtKB P00439
[16]
Resource
Comments
Medline ID
PubMed ID 9194198
Journal Protein Sci
Year 1997
Volume 6
Pages 1352-7
Authors Kobe B, Jennings IG, House CM, Feil SC, Michell BJ, Tiganis T, Parker MW, Cotton RG, Kemp BE
Title Regulation and crystallization of phosphorylated and dephosphorylated forms of truncated dimeric phenylalanine hydroxylase.
Related PDB
Related UniProtKB
[17]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 117-424
Medline ID 99060040
PubMed ID 9843368
Journal Biochemistry
Year 1998
Volume 37
Pages 15638-46
Authors Erlandsen H, Flatmark T, Stevens RC, Hough E
Title Crystallographic analysis of the human phenylalanine hydroxylase catalytic domain with bound catechol inhibitors at 2.0 A resolution.
Related PDB 3pah 4pah 5pah 6pah
Related UniProtKB P00439
[18]
Resource
Comments
Medline ID
PubMed ID 9540801
Journal Biochim Biophys Acta
Year 1998
Volume 1382
Pages 295-304
Authors Hufton SE, Jennings IG, Cotton RG
Title Structure/function analysis of the domains required for the multimerisation of phenylalanine hydroxylase.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 9799096
Journal Eur J Biochem
Year 1998
Volume 257
Pages 1-10
Authors Bjorgo E, Knappskog PM, Martinez A, Stevens RC, Flatmark T
Title Partial characterization and three-dimensional-structural localization of eight mutations in exon 7 of the human phenylalanine hydroxylase gene associated with phenylketonuria.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 9490012
Journal FEBS Lett
Year 1998
Volume 422
Pages 225-30
Authors Chehin R, Thorolfsson M, Knappskog PM, Martinez A, Flatmark T, Arrondo JL, Muga A
Title Domain structure and stability of human phenylalanine hydroxylase inferred from infrared spectroscopy.
Related PDB
Related UniProtKB
[21]
Resource
Comments CHARACTERIZATION OF VARIANTS
Medline ID 98111373
PubMed ID 9450897
Journal Hum Mutat
Year 1998
Volume 11
Pages 4-17
Authors Waters PJ, Parniak MA, Nowacki P, Scriver CR
Title In vitro expression analysis of mutations in phenylalanine hydroxylase: linking genotype to phenotype and structure to function.
Related PDB
Related UniProtKB P00439
[22]
Resource
Comments X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 117-452
Medline ID 98307935
PubMed ID 9642259
Journal J Biol Chem
Year 1998
Volume 273
Pages 16962-7
Authors Fusetti F, Erlandsen H, Flatmark T, Stevens RC
Title Structure of tetrameric human phenylalanine hydroxylase and its implications for phenylketonuria.
Related PDB 2pah
Related UniProtKB P00439
[23]
Resource
Comments
Medline ID
PubMed ID 9846749
Journal Microbiology
Year 1998
Volume 144
Pages 3127-34
Authors Gu W, Song J, Bonner CA, Xie G, Jensen RA
Title PhhC is an essential aminotransferase for aromatic amino acid catabolism in Pseudomonas aeruginosa.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 10037716
Journal J Biol Chem
Year 1999
Volume 274
Pages 6280-4
Authors Olafsdottir S, Martinez A
Title The accessibility of iron at the active site of recombinant human phenylalanine hydroxylase to water as studied by 1H NMR paramagnetic relaxation. Effect of L-Phe and comparison with the rat enzyme.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 10610798
Journal J Mol Biol
Year 1999
Volume 294
Pages 807-23
Authors Teigen K, Froystein NA, Martinez A
Title The structural basis of the recognition of phenylalanine and pterin cofactors by phenylalanine hydroxylase: implications for the catalytic mechanism.
Related PDB
Related UniProtKB
[26]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS)
Medline ID 99260738
PubMed ID 10331871
Journal Nat Struct Biol
Year 1999
Volume 6
Pages 442-8
Authors Kobe B, Jennings IG, House CM, Michell BJ, Goodwill KE, Santarsiero BD, Stevens RC, Cotton RG, Kemp BE
Title Structural basis of autoregulation of phenylalanine hydroxylase.
Related PDB 1phz 2phm
Related UniProtKB P04176
[27]
Resource
Comments
Medline ID
PubMed ID 10331859
Journal Nat Struct Biol
Year 1999
Volume 6
Pages 401-2
Authors Vrana KE
Title How the regulatory and catalytic domains get together.
Related PDB
Related UniProtKB
[28]
Resource
Comments
Medline ID
PubMed ID 11368310
Journal Arch Biochem Biophys
Year 2000
Volume 384
Pages 238-44
Authors Jennings IG, Cotton RG, Kobe B
Title Functional analysis, using in vitro mutagenesis, of amino acids located in the phenylalanine hydroxylase active site.
Related PDB
Related UniProtKB
[29]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10694386
Journal Biochemistry
Year 2000
Volume 39
Pages 2208-17
Authors Erlandsen H, Bjorgo E, Flatmark T, Stevens RC
Title Crystal structure and site-specific mutagenesis of pterin-bound human phenylalanine hydroxylase.
Related PDB 1dmw
Related UniProtKB
[30]
Resource
Comments
Medline ID
PubMed ID 11012685
Journal Eur J Biochem
Year 2000
Volume 267
Pages 6302-10
Authors Solstad T, Flatmark T
Title Microheterogeneity of recombinant human phenylalanine hydroxylase as a result of nonenzymatic deamidations of labile amide containing amino acids. Effects on catalytic and stability properties.
Related PDB
Related UniProtKB
[31]
Resource
Comments
Medline ID
PubMed ID 10980574
Journal Eur J Hum Genet
Year 2000
Volume 8
Pages 683-96
Authors Jennings IG, Cotton RG, Kobe B
Title Structural interpretation of mutations in phenylalanine hydroxylase protein aids in identifying genotype-phenotype correlations in phenylketonuria.
Related PDB
Related UniProtKB
[32]
Resource
Comments CHARACTERIZATION OF VARIANTS PKU
Medline ID 21313102
PubMed ID 11326337
Journal Am J Hum Genet
Year 2001
Volume 68
Pages 1353-60
Authors Gjetting T, Petersen M, Guldberg P, Guttler F
Title Missense mutations in the N-terminal domain of human phenylalanine hydroxylase interfere with binding of regulatory phenylalanine.
Related PDB
Related UniProtKB P00439
[33]
Resource
Comments
Medline ID
PubMed ID 11444803
Journal Anal Biochem
Year 2001
Volume 294
Pages 95-101
Authors Flatmark T, Stokka AJ, Berge SV
Title Use of surface plasmon resonance for real-time measurements of the global conformational transition in human phenylalanine hydroxylase in response to substrate binding and catalytic activation.
Related PDB
Related UniProtKB
[34]
Resource
Comments
Medline ID
PubMed ID 11410294
Journal Biochim Biophys Acta
Year 2001
Volume 1547
Pages 379-86
Authors Doskeland AP, Flatmark T
Title Conjugation of phenylalanine hydroxylase with polyubiquitin chains catalysed by rat liver enzymes.
Related PDB
Related UniProtKB
[35]
Resource
Comments
Medline ID
PubMed ID 11179966
Journal Eur J Biochem
Year 2001
Volume 268
Pages 997-1005
Authors Bjorgo E, de Carvalho RM, Flatmark T
Title A comparison of kinetic and regulatory properties of the tetrameric and dimeric forms of wild-type and Thr427-->Pro mutant human phenylalanine hydroxylase: contribution of the flexible hinge region Asp425-Gln429 to the tetramerization and cooperative substrate binding.
Related PDB
Related UniProtKB
[36]
Resource
Comments
Medline ID
PubMed ID 11163771
Journal FEBS Lett
Year 2001
Volume 488
Pages 196-200
Authors Jennings IG, Teh T, Kobe B
Title Essential role of the N-terminal autoregulatory sequence in the regulation of phenylalanine hydroxylase.
Related PDB
Related UniProtKB
[37]
Resource
Comments
Medline ID
PubMed ID 11301319
Journal J Biol Chem
Year 2001
Volume 276
Pages 22850-6
Authors Hagedoorn PL, Schmidt PP, Andersson KK, Hagen WR, Flatmark T, Martinez A
Title The effect of substrate, dihydrobiopterin, and dopamine on the EPR spectroscopic properties and the midpoint potential of the catalytic iron in recombinant human phenylalanine hydroxylase.
Related PDB
Related UniProtKB
[38]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11718561
Journal J Mol Biol
Year 2001
Volume 314
Pages 279-91
Authors Andersen OA, Flatmark T, Hough E
Title High resolution crystal structures of the catalytic domain of human phenylalanine hydroxylase in its catalytically active Fe(II) form and binary complex with tetrahydrobiopterin.
Related PDB 1j8t 1j8u
Related UniProtKB
[39]
Resource
Comments
Medline ID
PubMed ID 11161839
Journal Mol Genet Metab
Year 2001
Volume 72
Pages 132-43
Authors Gjetting T, Petersen M, Guldberg P, Guttler F
Title In vitro expression of 34 naturally occurring mutant variants of phenylalanine hydroxylase: correlation with metabolic phenotypes and susceptibility toward protein aggregation.
Related PDB
Related UniProtKB
[40]
Resource
Comments
Medline ID
PubMed ID 11461190
Journal Mol Genet Metab
Year 2001
Volume 73
Pages 230-8
Authors Waters PJ, Scriver CR, Parniak MA
Title Homomeric and heteromeric interactions between wild-type and mutant phenylalanine hydroxylase subunits: evaluation of two-hybrid approaches for functional analysis of mutations causing hyperphenylalaninemia.
Related PDB
Related UniProtKB
[41]
Resource
Comments
Medline ID
PubMed ID 12056888
Journal Biochemistry
Year 2002
Volume 41
Pages 7573-85
Authors Thorolfsson M, Ibarra-Molero B, Fojan P, Petersen SB, Sanchez-Ruiz JM, Martinez A
Title L-phenylalanine binding and domain organization in human phenylalanine hydroxylase: a differential scanning calorimetry study.
Related PDB
Related UniProtKB
[42]
Resource
Comments
Medline ID
PubMed ID 12185072
Journal J Biol Chem
Year 2002
Volume 277
Pages 40937-43
Authors Miranda FF, Teigen K, Thorolfsson M, Svebak RM, Knappskog PM, Flatmark T, Martinez A
Title Phosphorylation and mutations of Ser(16) in human phenylalanine hydroxylase. Kinetic and structural effects.
Related PDB
Related UniProtKB
[43]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 12126628
Journal J Mol Biol
Year 2002
Volume 320
Pages 1095-108
Authors Andersen OA, Flatmark T, Hough E
Title 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.
Related PDB 1kw0
Related UniProtKB
[44]
Resource
Comments
Medline ID
PubMed ID 12096915
Journal J Mol Biol
Year 2002
Volume 320
Pages 645-61
Authors Erlandsen H, Kim JY, Patch MG, Han A, Volner A, Abu-Omar MM, Stevens RC
Title Structural comparison of bacterial and human iron-dependent phenylalanine hydroxylases: similar fold, different stability and reaction rates.
Related PDB
Related UniProtKB
[45]
Resource
Comments
Medline ID
PubMed ID 12142458
Journal Protein Sci
Year 2002
Volume 11
Pages 2041-7
Authors Horne J, Jennings IG, Teh T, Gooley PR, Kobe B
Title Structural characterization of the N-terminal autoregulatory sequence of phenylalanine hydroxylase.
Related PDB
Related UniProtKB
[46]
Resource
Comments
Medline ID
PubMed ID 12653545
Journal Biochemistry
Year 2003
Volume 42
Pages 3419-28
Authors Thorolfsson M, Teigen K, Martinez A
Title Activation of phenylalanine hydroxylase: effect of substitutions at Arg68 and Cys237.
Related PDB
Related UniProtKB
[47]
Resource
Comments
Medline ID
PubMed ID 12631267
Journal Eur J Biochem
Year 2003
Volume 270
Pages 1065-75
Authors Maass A, Scholz J, Moser A
Title Modeled ligand-protein complexes elucidate the origin of substrate specificity and provide insight into catalytic mechanisms of phenylalanine hydroxylase and tyrosine hydroxylase.
Related PDB
Related UniProtKB
[48]
Resource
Comments
Medline ID
PubMed ID 12603331
Journal Eur J Biochem
Year 2003
Volume 270
Pages 981-90
Authors Solstad T, Stokka AJ, Andersen OA, Flatmark T
Title Studies on the regulatory properties of the pterin cofactor and dopamine bound at the active site of human phenylalanine hydroxylase.
Related PDB
Related UniProtKB
[49]
Resource
Comments
Medline ID
PubMed ID 12655546
Journal Hum Mutat
Year 2003
Volume 21
Pages 370-8
Authors Pey AL, Desviat LR, Gamez A, Ugarte M, Perez B
Title Phenylketonuria: genotype-phenotype correlations based on expression analysis of structural and functional mutations in PAH.
Related PDB
Related UniProtKB
[50]
Resource
Comments
Medline ID
PubMed ID 12696880
Journal J Am Chem Soc
Year 2003
Volume 125
Pages 4710-1
Authors Kinzie SD, Thevis M, Ngo K, Whitelegge J, Loo JA, Abu-Omar MM
Title Posttranslational hydroxylation of human phenylalanine hydroxylase is a novel example of enzyme self-repair within the second coordination sphere of catalytic iron.
Related PDB
Related UniProtKB
[51]
Resource
Comments
Medline ID
PubMed ID 12554741
Journal J Biol Chem
Year 2003
Volume 278
Pages 15142-52
Authors Carvalho RN, Solstad T, Bjorgo E, Barroso JF, Flatmark T
Title Deamidations in recombinant human phenylalanine hydroxylase. Identification of labile asparagine residues and functional characterization of Asn --> Asp mutant forms.
Related PDB
Related UniProtKB
[52]
Resource
Comments
Medline ID
PubMed ID 14568534
Journal J Mol Biol
Year 2003
Volume 333
Pages 747-57
Authors Andersen OA, Stokka AJ, Flatmark T, Hough E
Title 2.0A 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.
Related PDB
Related UniProtKB
[53]
Resource
Comments
Medline ID
PubMed ID 15313177
Journal Biochem Biophys Res Commun
Year 2004
Volume 322
Pages 88-92
Authors Schallreuter KU, Wazir U, Kothari S, Gibbons NC, Moore J, Wood JM
Title Human phenylalanine hydroxylase is activated by H2O2: a novel mechanism for increasing the L-tyrosine supply for melanogenesis in melanocytes.
Related PDB
Related UniProtKB
[54]
Resource
Comments
Medline ID
PubMed ID 15060071
Journal J Biol Chem
Year 2004
Volume 279
Pages 26571-80
Authors Stokka AJ, Carvalho RN, Barroso JF, Flatmark T
Title 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.
Related PDB
Related UniProtKB
[55]
Resource
Comments
Medline ID
PubMed ID 15557004
Journal Proc Natl Acad Sci U S A
Year 2004
Volume 101
Pages 16903-8
Authors Erlandsen H, Pey AL, Gamez A, Perez B, Desviat LR, Aguado C, Koch R, Surendran S, Tyring S, Matalon R, Scriver CR, Ugarte M, Martinez A, Stevens RC
Title Correction of kinetic and stability defects by tetrahydrobiopterin in phenylketonuria patients with certain phenylalanine hydroxylase mutations.
Related PDB 1tdw 1tg2
Related UniProtKB

Comments
This enzyme is composed of the N-terminal regulatory domain and the C-terminal catalytic domain.
This enzyme catalyzes the following reaction:
(A) Sequential Oxygenation of Tetrahydrobiopterin and L-Phenylalanine by O2, giving 4a-hydroxytetrahydrobiopterin and L-Tyrosine:

Created Updated
2004-01-27 2009-02-26