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) |
|---|---|
| 1.10.800.10 : Phenylalanine Hydroxylase | D00478 |
| 3.30.70.260 : Alpha-Beta Plaits | T00247 |
| 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 |
|---|---|---|---|---|---|
| P04176 | PH4H_RAT | L-phenylalanine + tetrahydrobiopterin + O(2) = L-tyrosine + 4a-hydroxytetrahydrobiopterin. | Homodimer. | Fe(2+) ion. | |
| P00439 | PH4H_HUMAN | 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 18248 82664 |
17295 58095 17295 58095 |
59560 59560 |
15379 26689 27140 15379 26689 27140 |
17895 58315 17895 58315 |
|||||||
| PubChem |
23925 23925 |
6140 6925665 6140 6925665 |
44257 44257 |
977 977 |
6057 6942100 6057 6942100 |
46173804 46173804 |
||||||
| 1phzA01 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 2phmA01 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1dmwA |
|
|
|
|
|
Bound:_FE | Unbound | Analogue:HBI | Unbound | Unbound | Unbound | |
| 1j8tA |
|
|
|
|
|
Bound:FE2 | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1j8uA |
|
|
|
|
|
Bound:FE2 | Unbound | Bound:H4B | Unbound | Unbound | Unbound | |
| 1kw0A |
|
|
|
|
|
Bound:FE2 | Analogue:TIH | Bound:H4B | Analogue:HOH_435 | Unbound | Unbound | |
| 1lrmA |
|
|
|
|
|
Bound:_FE | Unbound | Analogue:HBI | Unbound | Unbound | Unbound | |
| 1mmkA |
|
|
|
|
|
Bound:FE2 | Analogue:TIH | Bound:H4B | Unbound | Unbound | Unbound | |
| 1mmtA |
|
|
|
|
|
Bound:FE2 | Analogue:NLE | Bound:H4B | Analogue:HOH_575 | Unbound | Unbound | |
| 1pahA |
|
|
|
|
|
Bound:_FE | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1tdwA |
|
|
|
|
|
Bound:_FE | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1tg2A |
|
|
|
|
|
Bound:_FE | Unbound | Analogue:H2B | Unbound | Unbound | Unbound | |
| 2pahA |
|
|
|
|
|
Bound:_FE | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 2pahB |
|
|
|
|
|
Bound:_FE | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3pahA |
|
|
|
|
|
Bound:_FE | Unbound | Unbound | Unbound | Analogue:ALE | Unbound | |
| 4pahA |
|
|
|
|
|
Bound:_FE | Unbound | Unbound | Unbound | Analogue:LNR | Unbound | |
| 5pahA |
|
|
|
|
|
Bound:_FE | Unbound | Unbound | Unbound | Analogue:LDP | Unbound | |
| 6pahA |
|
|
|
|
|
Bound:_FE | Unbound | Unbound | Unbound | Analogue:DAH | Unbound | |
| 1phzA02 |
|
|
|
|
|
Bound:_FE | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 2phmA02 |
|
|
|
|
|
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 |
|
|
|
|
|
(phospholylation) | invisible S16 (phosphorylation site) | |||
| 2phmA01 |
|
|
|
|
|
(phospholylation) | invisible S16 (phosphorylation site) | |||
| 1dmwA |
|
|
|
|
|
HIS 285;HIS 290;GLU 330(Iron binding) | ||||
| 1j8tA |
|
|
|
|
|
HIS 285;HIS 290;GLU 330(Iron binding) | ||||
| 1j8uA |
|
|
|
|
|
HIS 285;HIS 290;GLU 330(Iron binding) | ||||
| 1kw0A |
|
|
|
|
|
HIS 285;HIS 290;GLU 330(Iron binding) | ||||
| 1lrmA |
|
|
|
|
|
HIS 285;HIS 290;GLU 330(Iron binding) | ||||
| 1mmkA |
|
|
|
|
|
HIS 285;HIS 290;GLU 330(Iron binding) | ||||
| 1mmtA |
|
|
|
|
|
HIS 285;HIS 290;GLU 330(Iron binding) | ||||
| 1pahA |
|
|
|
|
|
HIS 285;HIS 290;GLU 330(Iron binding) | ||||
| 1tdwA |
|
|
|
|
|
HIS 285;HIS 290;GLU 330(Iron binding) | ||||
| 1tg2A |
|
|
|
|
|
HIS 285;HIS 290;GLU 330(Iron binding) | ||||
| 2pahA |
|
|
|
|
|
HIS 285;HIS 290;GLU 330(Iron binding) | ||||
| 2pahB |
|
|
|
|
|
HIS 285;HIS 290;GLU 330(Iron binding) | ||||
| 3pahA |
|
|
|
|
|
HIS 285;HIS 290;GLU 330(Iron binding) | ||||
| 4pahA |
|
|
|
|
|
HIS 285;HIS 290;GLU 330(Iron binding) | ||||
| 5pahA |
|
|
|
|
|
HIS 285;HIS 290;GLU 330(Iron binding) | ||||
| 6pahA |
|
|
|
|
|
HIS 285;HIS 290;GLU 330(Iron binding) | ||||
| 1phzA02 |
|
|
|
|
|
HIS 285;HIS 290;GLU 330(Iron binding) | ||||
| 2phmA02 |
|
|
|
|
|
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, |
| 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, |
| 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. |
| 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, |
| 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. |
| 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, |
| 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. |
| 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, |
| 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, |
| 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. |
| 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, |
| Created | Updated |
|---|---|
| 2004-01-27 | 2009-02-26 |