EzCatDB: D00496
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DB codeD00496
CATH domainDomain 13.30.70.260 : Alpha-Beta Plaits
Domain 21.10.800.10 : Phenylalanine HydroxylaseCatalytic domain
E.C.1.14.16.1

CATH domainRelated DB codes (homologues)
1.10.800.10 : Phenylalanine HydroxylaseD00478
3.30.70.260 : Alpha-Beta PlaitsT00247

Enzyme Name
UniProtKBKEGG

P04176P00439
Protein namePhenylalanine-4-hydroxylasePhenylalanine-4-hydroxylasephenylalanine 4-monooxygenase
phenylalaninase
phenylalanine 4-hydroxylase
phenylalanine hydroxylase
SynonymsPAH
EC 1.14.16.1
Phe-4-monooxygenase
PAH
EC 1.14.16.1
Phe-4-monooxygenase
RefSeq
NP_000268.1 (Protein)
NM_000277.1 (DNA/RNA sequence)
PfamPF01842 (ACT)
PF00351 (Biopterin_H)
[Graphical view]
PF01842 (ACT)
PF00351 (Biopterin_H)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00400Phenylalanine, tyrosine and tryptophan biosynthesis

UniProtKB:Accession NumberP04176P00439
Entry namePH4H_RATPH4H_HUMAN
ActivityL-phenylalanine + tetrahydrobiopterin + O(2) = L-tyrosine + 4a-hydroxytetrahydrobiopterin.L-phenylalanine + tetrahydrobiopterin + O(2) = L-tyrosine + 4a-hydroxytetrahydrobiopterin.
SubunitHomodimer.Homodimer.
Subcellular location

CofactorFe(2+) ion.Fe(2+) ion.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00023C00079C00272C00007C00082C15522
CompoundIronL-PhenylalanineTetrahydrobiopterinO2L-Tyrosine4a-hydroxytetrahydrobiopterin
Typeheavy metalamino acids,aromatic ring (only carbon atom)amide group,amine group,aromatic ring (with nitrogen atoms),carbohydrateothersamino acids,aromatic ring (only carbon atom)amine group,aromatic ring (with nitrogen atoms),carbohydrate
ChEBI18248
82664
17295
58095
59560
27140
26689
15379
17895
58315

PubChem23925
6925665
6140
44257
977
6942100
6057
46173804
              
1phzA01UnboundUnboundUnboundUnboundUnboundUnbound
2phmA01UnboundUnboundUnboundUnboundUnboundUnbound
1dmwABound:_FEUnboundAnalogue:HBIUnboundUnboundUnbound
1j8tABound:FE2UnboundUnboundUnboundUnboundUnbound
1j8uABound:FE2UnboundBound:H4BUnboundUnboundUnbound
1kw0ABound:FE2Analogue:TIHBound:H4BAnalogue:HOH 435UnboundUnbound
1lrmABound:_FEUnboundAnalogue:HBIUnboundUnboundUnbound
1mmkABound:FE2Analogue:TIHBound:H4BUnboundUnboundUnbound
1mmtABound:FE2Analogue:NLEBound:H4BAnalogue:HOH 575UnboundUnbound
1pahABound:_FEUnboundUnboundUnboundUnboundUnbound
1tdwABound:_FEUnboundUnboundUnboundUnboundUnbound
1tg2ABound:_FEUnboundAnalogue:H2BUnboundUnboundUnbound
2pahABound:_FEUnboundUnboundUnboundUnboundUnbound
2pahBBound:_FEUnboundUnboundUnboundUnboundUnbound
3pahABound:_FEUnboundUnboundUnboundAnalogue:ALEUnbound
4pahABound:_FEUnboundUnboundUnboundAnalogue:LNRUnbound
5pahABound:_FEUnboundUnboundUnboundAnalogue:LDPUnbound
6pahABound:_FEUnboundUnboundUnboundAnalogue:DAHUnbound
1phzA02Bound:_FEUnboundUnboundUnboundUnboundUnbound
2phmA02Bound:_FEUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
PDB;1pah & Swiss-prot;P00439, P04176
pdbCofactor-binding residuesModified residuescomment
           
1phzA01 
      (phospholylation)
invisible S16 (phosphorylation site)
2phmA01 
      (phospholylation)
invisible S16 (phosphorylation site)
1dmwAHIS 285;HIS 290;GLU 330(Iron binding)
 
 
1j8tAHIS 285;HIS 290;GLU 330(Iron binding)
 
 
1j8uAHIS 285;HIS 290;GLU 330(Iron binding)
 
 
1kw0AHIS 285;HIS 290;GLU 330(Iron binding)
 
 
1lrmAHIS 285;HIS 290;GLU 330(Iron binding)
 
 
1mmkAHIS 285;HIS 290;GLU 330(Iron binding)
 
 
1mmtAHIS 285;HIS 290;GLU 330(Iron binding)
 
 
1pahAHIS 285;HIS 290;GLU 330(Iron binding)
 
 
1tdwAHIS 285;HIS 290;GLU 330(Iron binding)
 
 
1tg2AHIS 285;HIS 290;GLU 330(Iron binding)
 
 
2pahAHIS 285;HIS 290;GLU 330(Iron binding)
 
 
2pahBHIS 285;HIS 290;GLU 330(Iron binding)
 
 
3pahAHIS 285;HIS 290;GLU 330(Iron binding)
 
 
4pahAHIS 285;HIS 290;GLU 330(Iron binding)
 
 
5pahAHIS 285;HIS 290;GLU 330(Iron binding)
 
 
6pahAHIS 285;HIS 290;GLU 330(Iron binding)
 
 
1phzA02HIS 285;HIS 290;GLU 330(Iron binding)
 
 
2phmA02HIS 285;HIS 290;GLU 330(Iron binding)
 
 

References for Catalytic Mechanism
ReferencesSectionsNo. 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]
PubMed ID4087300
JournalJ Mol Biol
Year1985
Volume186
Pages479-80
AuthorsGuddat LW, Cowan SW, Machin KJ, Isaacs NW, Cotton RG
TitleCrystallization and preliminary crystallographic data of the Fab fragment of an anti-phenylalanine hydroxylase monoclonal antibody.
[2]
PubMed ID3769914
JournalEur J Biochem
Year1986
Volume160
Pages1-8
AuthorsHaavik J, Doskeland AP, Flatmark T
TitleStereoselective effects in the interactions of pterin cofactors with rat-liver phenylalanine 4-monooxygenase.
[3]
CommentsREVIEW ON PKU VARIANTS
Medline ID91061429
PubMed ID2246858
JournalJ Inherit Metab Dis
Year1990
Volume13
Pages739-50
AuthorsCotton RG
TitleHeterogeneity of phenylketonuria at the clinical, protein and DNA levels.
Related UniProtKBP00439
[4]
PubMed ID1681899
JournalBiochemistry
Year1991
Volume30
Pages10226-35
AuthorsBailey SW, Dillard SB, Ayling JE
TitleRole of C6 chirality of tetrahydropterin cofactor in catalysis and regulation of tyrosine and phenylalanine hydroxylases.
[5]
PubMed ID1646718
JournalEur J Biochem
Year1991
Volume198
Pages675-82
AuthorsMartinez A, Andersson KK, Haavik J, Flatmark T
TitleEPR and 1H-NMR spectroscopic studies on the paramagnetic iron at the active site of phenylalanine hydroxylase and its interaction with substrates and inhibitors.
[6]
CommentsREVIEW ON PKU VARIANTS
Medline ID91348681
PubMed ID1679029
JournalHum Genet
Year1991
Volume87
Pages377-88
AuthorsKonecki DS, Lichter-Konecki U
TitleThe phenylketonuria locus: current knowledge about alleles and mutations of the phenylalanine hydroxylase gene in various populations.
Related UniProtKBP00439
[7]
PubMed ID2016740
JournalJ Mol Biol
Year1991
Volume218
Pages495-8
AuthorsCelikel R, Davis MD, Dai XP, Kaufman S, Xuong NH
TitleCrystallization and preliminary X-ray analysis of phenylalanine hydroxylase from rat liver.
[8]
CommentsREVIEW ON PKU VARIANTS
Medline ID93244826
PubMed ID1301187
JournalHum Mutat
Year1992
Volume1
Pages13-23
AuthorsEisensmith RC, Woo SL
TitleMolecular basis of phenylketonuria and related hyperphenylalaninemias: mutations and polymorphisms in the human phenylalanine hydroxylase gene.
Related UniProtKBP00439
[9]
PubMed ID8031788
JournalBiochemistry
Year1994
Volume33
Pages8532-7
AuthorsBalasubramanian S, Carr RT, Bender CJ, Peisach J, Benkovic SJ
TitleIdentification of metal ligands in Cu(II)-inhibited Chromobacterium violaceum phenylalanine hydroxylase by electron spin echo envelope modulation analysis of histidine to serine mutations.
[10]
PubMed ID7914195
JournalJ Biol Chem
Year1994
Volume269
Pages20369-75
AuthorsDickson PW, Jennings IG, Cotton RG
TitleDelineation of the catalytic core of phenylalanine hydroxylase and identification of glutamate 286 as a critical residue for pterin function.
[11]
PubMed ID8573072
JournalBiochem J
Year1996
Volume313
Pages409-14
AuthorsDoskeland AP, Martinez A, Knappskog PM, Flatmark T
TitlePhosphorylation of recombinant human phenylalanine hydroxylase: effect on catalytic activity, substrate activation and protection against non-specific cleavage of the fusion protein by restriction protease.
[12]
CommentsCHARACTERIZATION OF VARIANT PKU GLY-143
Medline ID9704451
PubMed ID8889583
JournalHum Mutat
Year1996
Volume8
Pages236-46
AuthorsKnappskog PM, Eiken HG, Martinez A, Bruland O, Apold J, Flatmark T
TitlePKU mutation (D143G) associated with an apparent high residual enzyme activity: expression of a kinetic variant form of phenylalanine hydroxylase in three different systems.
Related UniProtKBP00439
[13]
PubMed ID9434741
JournalArch Biochem Biophys
Year1997
Volume348
Pages295-302
AuthorsDaubner SC, Hillas PJ, Fitzpatrick PF
TitleExpression and characterization of the catalytic domain of human phenylalanine hydroxylase.
[14]
PubMed ID9109411
JournalFEBS Lett
Year1997
Volume406
Pages171-4
AuthorsErlandsen H, Martinez A, Knappskog PM, Haavik J, Hough E, Flatmark T
TitleCrystallization and preliminary diffraction analysis of a truncated homodimer of human phenylalanine hydroxylase.
[15]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 117-424
Medline ID98069646
PubMed ID9406548
JournalNat Struct Biol
Year1997
Volume4
Pages995-1000
AuthorsErlandsen H, Fusetti F, Martinez A, Hough E, Flatmark T, Stevens RC
TitleCrystal structure of the catalytic domain of human phenylalanine hydroxylase reveals the structural basis for phenylketonuria.
Related PDB1pah
Related UniProtKBP00439
[16]
PubMed ID9194198
JournalProtein Sci
Year1997
Volume6
Pages1352-7
AuthorsKobe B, Jennings IG, House CM, Feil SC, Michell BJ, Tiganis T, Parker MW, Cotton RG, Kemp BE
TitleRegulation and crystallization of phosphorylated and dephosphorylated forms of truncated dimeric phenylalanine hydroxylase.
[17]
CommentsX-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 117-424
Medline ID99060040
PubMed ID9843368
JournalBiochemistry
Year1998
Volume37
Pages15638-46
AuthorsErlandsen H, Flatmark T, Stevens RC, Hough E
TitleCrystallographic analysis of the human phenylalanine hydroxylase catalytic domain with bound catechol inhibitors at 2.0 A resolution.
Related PDB3pah,4pah,5pah,6pah
Related UniProtKBP00439
[18]
PubMed ID9540801
JournalBiochim Biophys Acta
Year1998
Volume1382
Pages295-304
AuthorsHufton SE, Jennings IG, Cotton RG
TitleStructure/function analysis of the domains required for the multimerisation of phenylalanine hydroxylase.
[19]
PubMed ID9799096
JournalEur J Biochem
Year1998
Volume257
Pages1-10
AuthorsBjorgo E, Knappskog PM, Martinez A, Stevens RC, Flatmark T
TitlePartial characterization and three-dimensional-structural localization of eight mutations in exon 7 of the human phenylalanine hydroxylase gene associated with phenylketonuria.
[20]
PubMed ID9490012
JournalFEBS Lett
Year1998
Volume422
Pages225-30
AuthorsChehin R, Thorolfsson M, Knappskog PM, Martinez A, Flatmark T, Arrondo JL, Muga A
TitleDomain structure and stability of human phenylalanine hydroxylase inferred from infrared spectroscopy.
[21]
CommentsCHARACTERIZATION OF VARIANTS
Medline ID98111373
PubMed ID9450897
JournalHum Mutat
Year1998
Volume11
Pages4-17
AuthorsWaters PJ, Parniak MA, Nowacki P, Scriver CR
TitleIn vitro expression analysis of mutations in phenylalanine hydroxylase: linking genotype to phenotype and structure to function.
Related UniProtKBP00439
[22]
CommentsX-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 117-452
Medline ID98307935
PubMed ID9642259
JournalJ Biol Chem
Year1998
Volume273
Pages16962-7
AuthorsFusetti F, Erlandsen H, Flatmark T, Stevens RC
TitleStructure of tetrameric human phenylalanine hydroxylase and its implications for phenylketonuria.
Related PDB2pah
Related UniProtKBP00439
[23]
PubMed ID9846749
JournalMicrobiology
Year1998
Volume144
Pages3127-34
AuthorsGu W, Song J, Bonner CA, Xie G, Jensen RA
TitlePhhC is an essential aminotransferase for aromatic amino acid catabolism in Pseudomonas aeruginosa.
[24]
PubMed ID10037716
JournalJ Biol Chem
Year1999
Volume274
Pages6280-4
AuthorsOlafsdottir S, Martinez A
TitleThe 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.
[25]
PubMed ID10610798
JournalJ Mol Biol
Year1999
Volume294
Pages807-23
AuthorsTeigen K, Froystein NA, Martinez A
TitleThe structural basis of the recognition of phenylalanine and pterin cofactors by phenylalanine hydroxylase: implications for the catalytic mechanism.
[26]
CommentsX-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS)
Medline ID99260738
PubMed ID10331871
JournalNat Struct Biol
Year1999
Volume6
Pages442-8
AuthorsKobe B, Jennings IG, House CM, Michell BJ, Goodwill KE, Santarsiero BD, Stevens RC, Cotton RG, Kemp BE
TitleStructural basis of autoregulation of phenylalanine hydroxylase.
Related PDB1phz,2phm
Related UniProtKBP04176
[27]
PubMed ID10331859
JournalNat Struct Biol
Year1999
Volume6
Pages401-2
AuthorsVrana KE
TitleHow the regulatory and catalytic domains get together.
[28]
PubMed ID11368310
JournalArch Biochem Biophys
Year2000
Volume384
Pages238-44
AuthorsJennings IG, Cotton RG, Kobe B
TitleFunctional analysis, using in vitro mutagenesis, of amino acids located in the phenylalanine hydroxylase active site.
[29]
CommentsX-ray crystallography
PubMed ID10694386
JournalBiochemistry
Year2000
Volume39
Pages2208-17
AuthorsErlandsen H, Bjorgo E, Flatmark T, Stevens RC
TitleCrystal structure and site-specific mutagenesis of pterin-bound human phenylalanine hydroxylase.
Related PDB1dmw
[30]
PubMed ID11012685
JournalEur J Biochem
Year2000
Volume267
Pages6302-10
AuthorsSolstad T, Flatmark T
TitleMicroheterogeneity of recombinant human phenylalanine hydroxylase as a result of nonenzymatic deamidations of labile amide containing amino acids. Effects on catalytic and stability properties.
[31]
PubMed ID10980574
JournalEur J Hum Genet
Year2000
Volume8
Pages683-96
AuthorsJennings IG, Cotton RG, Kobe B
TitleStructural interpretation of mutations in phenylalanine hydroxylase protein aids in identifying genotype-phenotype correlations in phenylketonuria.
[32]
CommentsCHARACTERIZATION OF VARIANTS PKU
Medline ID21313102
PubMed ID11326337
JournalAm J Hum Genet
Year2001
Volume68
Pages1353-60
AuthorsGjetting T, Petersen M, Guldberg P, Guttler F
TitleMissense mutations in the N-terminal domain of human phenylalanine hydroxylase interfere with binding of regulatory phenylalanine.
Related UniProtKBP00439
[33]
PubMed ID11444803
JournalAnal Biochem
Year2001
Volume294
Pages95-101
AuthorsFlatmark T, Stokka AJ, Berge SV
TitleUse 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.
[34]
PubMed ID11410294
JournalBiochim Biophys Acta
Year2001
Volume1547
Pages379-86
AuthorsDoskeland AP, Flatmark T
TitleConjugation of phenylalanine hydroxylase with polyubiquitin chains catalysed by rat liver enzymes.
[35]
PubMed ID11179966
JournalEur J Biochem
Year2001
Volume268
Pages997-1005
AuthorsBjorgo E, de Carvalho RM, Flatmark T
TitleA 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.
[36]
PubMed ID11163771
JournalFEBS Lett
Year2001
Volume488
Pages196-200
AuthorsJennings IG, Teh T, Kobe B
TitleEssential role of the N-terminal autoregulatory sequence in the regulation of phenylalanine hydroxylase.
[37]
PubMed ID11301319
JournalJ Biol Chem
Year2001
Volume276
Pages22850-6
AuthorsHagedoorn PL, Schmidt PP, Andersson KK, Hagen WR, Flatmark T, Martinez A
TitleThe effect of substrate, dihydrobiopterin, and dopamine on the EPR spectroscopic properties and the midpoint potential of the catalytic iron in recombinant human phenylalanine hydroxylase.
[38]
CommentsX-ray crystallography
PubMed ID11718561
JournalJ Mol Biol
Year2001
Volume314
Pages279-91
AuthorsAndersen OA, Flatmark T, Hough E
TitleHigh resolution crystal structures of the catalytic domain of human phenylalanine hydroxylase in its catalytically active Fe(II) form and binary complex with tetrahydrobiopterin.
Related PDB1j8t,1j8u
[39]
PubMed ID11161839
JournalMol Genet Metab
Year2001
Volume72
Pages132-43
AuthorsGjetting T, Petersen M, Guldberg P, Guttler F
TitleIn vitro expression of 34 naturally occurring mutant variants of phenylalanine hydroxylase: correlation with metabolic phenotypes and susceptibility toward protein aggregation.
[40]
PubMed ID11461190
JournalMol Genet Metab
Year2001
Volume73
Pages230-8
AuthorsWaters PJ, Scriver CR, Parniak MA
TitleHomomeric and heteromeric interactions between wild-type and mutant phenylalanine hydroxylase subunits: evaluation of two-hybrid approaches for functional analysis of mutations causing hyperphenylalaninemia.
[41]
PubMed ID12056888
JournalBiochemistry
Year2002
Volume41
Pages7573-85
AuthorsThorolfsson M, Ibarra-Molero B, Fojan P, Petersen SB, Sanchez-Ruiz JM, Martinez A
TitleL-phenylalanine binding and domain organization in human phenylalanine hydroxylase: a differential scanning calorimetry study.
[42]
PubMed ID12185072
JournalJ Biol Chem
Year2002
Volume277
Pages40937-43
AuthorsMiranda FF, Teigen K, Thorolfsson M, Svebak RM, Knappskog PM, Flatmark T, Martinez A
TitlePhosphorylation and mutations of Ser(16) in human phenylalanine hydroxylase. Kinetic and structural effects.
[43]
CommentsX-ray crystallography
PubMed ID12126628
JournalJ Mol Biol
Year2002
Volume320
Pages1095-108
AuthorsAndersen OA, Flatmark T, Hough E
TitleCrystal 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 PDB1kw0
[44]
PubMed ID12096915
JournalJ Mol Biol
Year2002
Volume320
Pages645-61
AuthorsErlandsen H, Kim JY, Patch MG, Han A, Volner A, Abu-Omar MM, Stevens RC
TitleStructural comparison of bacterial and human iron-dependent phenylalanine hydroxylases: similar fold, different stability and reaction rates.
[45]
PubMed ID12142458
JournalProtein Sci
Year2002
Volume11
Pages2041-7
AuthorsHorne J, Jennings IG, Teh T, Gooley PR, Kobe B
TitleStructural characterization of the N-terminal autoregulatory sequence of phenylalanine hydroxylase.
[46]
PubMed ID12653545
JournalBiochemistry
Year2003
Volume42
Pages3419-28
AuthorsThorolfsson M, Teigen K, Martinez A
TitleActivation of phenylalanine hydroxylase: effect of substitutions at Arg68 and Cys237.
[47]
PubMed ID12631267
JournalEur J Biochem
Year2003
Volume270
Pages1065-75
AuthorsMaass A, Scholz J, Moser A
TitleModeled ligand-protein complexes elucidate the origin of substrate specificity and provide insight into catalytic mechanisms of phenylalanine hydroxylase and tyrosine hydroxylase.
[48]
PubMed ID12603331
JournalEur J Biochem
Year2003
Volume270
Pages981-90
AuthorsSolstad T, Stokka AJ, Andersen OA, Flatmark T
TitleStudies on the regulatory properties of the pterin cofactor and dopamine bound at the active site of human phenylalanine hydroxylase.
[49]
PubMed ID12655546
JournalHum Mutat
Year2003
Volume21
Pages370-8
AuthorsPey AL, Desviat LR, Gamez A, Ugarte M, Perez B
TitlePhenylketonuria: genotype-phenotype correlations based on expression analysis of structural and functional mutations in PAH.
[50]
PubMed ID12696880
JournalJ Am Chem Soc
Year2003
Volume125
Pages4710-1
AuthorsKinzie SD, Thevis M, Ngo K, Whitelegge J, Loo JA, Abu-Omar MM
TitlePosttranslational hydroxylation of human phenylalanine hydroxylase is a novel example of enzyme self-repair within the second coordination sphere of catalytic iron.
[51]
PubMed ID12554741
JournalJ Biol Chem
Year2003
Volume278
Pages15142-52
AuthorsCarvalho RN, Solstad T, Bjorgo E, Barroso JF, Flatmark T
TitleDeamidations in recombinant human phenylalanine hydroxylase. Identification of labile asparagine residues and functional characterization of Asn --> Asp mutant forms.
[52]
PubMed ID14568534
JournalJ Mol Biol
Year2003
Volume333
Pages747-57
AuthorsAndersen OA, Stokka AJ, Flatmark T, Hough E
Title2.0A 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.
[53]
PubMed ID15313177
JournalBiochem Biophys Res Commun
Year2004
Volume322
Pages88-92
AuthorsSchallreuter KU, Wazir U, Kothari S, Gibbons NC, Moore J, Wood JM
TitleHuman phenylalanine hydroxylase is activated by H2O2: a novel mechanism for increasing the L-tyrosine supply for melanogenesis in melanocytes.
[54]
PubMed ID15060071
JournalJ Biol Chem
Year2004
Volume279
Pages26571-80
AuthorsStokka AJ, Carvalho RN, Barroso JF, Flatmark T
TitleProbing 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.
[55]
PubMed ID15557004
JournalProc Natl Acad Sci U S A
Year2004
Volume101
Pages16903-8
AuthorsErlandsen 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
TitleCorrection of kinetic and stability defects by tetrahydrobiopterin in phenylketonuria patients with certain phenylalanine hydroxylase mutations.
Related PDB1tdw,1tg2

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:

createdupdated
2004-01-272009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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