EC 1.14.16.1 - Phenylalanine 4-monooxygenase

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IntEnz Enzyme Nomenclature
EC 1.14.16.1

Names

Accepted name:
phenylalanine 4-monooxygenase
Other names:
phenylalaninase
phenylalanine 4-hydroxylase
phenylalanine hydroxylase
PAH
Systematic name:
L-phenylalanine,tetrahydrobiopterin:oxygen oxidoreductase (4-hydroxylating)

Reaction

Cofactor

Comments:

The active centre contains mononuclear iron(II). The reaction involves an arene oxide that rearranges to give the phenolic hydroxy group. This results in the hydrogen at C-4 migrating to C-3 and in part being retained. This process is known as the NIH-shift. The 4a-hydroxytetrahydrobiopterin formed can dehydrate to 6,7-dihydrobiopterin, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydrobiopterin can be enzymically reduced back to tetrahydrobiopterin, by EC 1.5.1.34, 6,7-dihydropteridine reductase, or slowly rearranges into the more stable compound 7,8-dihydrobiopterin.

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , DIAGRAM , DIAGRAM , DIAGRAM , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , UniPathway
Protein domains and families: PROSITE:PDOC00316
Structural data: CSA , EC2PDB
Gene Ontology: GO:0004505
CAS Registry Number: 9029-73-6
UniProtKB/Swiss-Prot: (13) [show] [UniProt]

References

  1. Guroff, G. and Rhoads, C.A.
    Phenylalanine hydroxylation by Pseudomonas species (ATCC 11299a). Nature of the cofactor.
    J. Biol. Chem. 244: 142-146 (1969). [PMID: 5773277]
  2. Kaufman, S.
    Studies on the mechanism of the enzymic conversion of phenylalanine to tyrosine.
    J. Biol. Chem. 234: 2677-2682 (1959).
  3. Mitoma, C.
    Studies on partially purified phenylalanine hydroxylase.
    Arch. Biochem. Biophys. 60: 476-484 (1956).
  4. Udenfriend, S. and Cooper, J.R.
    The enzymic conversion of phenylalanine to tyrosine.
    J. Biol. Chem. 194: 503-511 (1952).
  5. Carr, R.T., Balasubramanian, S., Hawkins, P.C. and Benkovic, S.J.
    Mechanism of metal-independent hydroxylation by Chromobacterium violaceum phenylalanine hydroxylase.
    Biochemistry 34: 7525-7532 (1995). [PMID: 7779797]
  6. Andersen, O.A., Flatmark, T. and 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. 314: 266-278 (2001). [PMID: 11718561]
  7. Erlandsen, H., Kim, J.Y., Patch, M.G., Han, A., Volner, A., Abu-Omar, M.M. and Stevens, R.C.
    Structural comparison of bacterial and human iron-dependent phenylalanine hydroxylases: similar fold, different stability and reaction rates.
    J. Mol. Biol. 320: 645-661 (2002). [PMID: 12096915]

[EC 1.14.16.1 created 1961 as EC 1.99.1.2, transferred 1965 to EC 1.14.3.1, transferred 1972 to EC 1.14.16.1, modified 2002, modified 2003]