2PHM
STRUCTURE OF PHENYLALANINE HYDROXYLASE DEPHOSPHORYLATED
Summary for 2PHM
| Entry DOI | 10.2210/pdb2phm/pdb |
| Descriptor | PROTEIN (PHENYLALANINE-4-HYDROXYLASE), FE (III) ION (3 entities in total) |
| Functional Keywords | phenylalanine hydroxylase, aromatic amino acid hydroxylase, phosphorylation, intrasteric regulation, allosteric regulation, oxidoreductase |
| Biological source | Rattus norvegicus (Norway rat) |
| Total number of polymer chains | 1 |
| Total formula weight | 49385.39 |
| Authors | Kobe, B.,Jennings, I.G.,House, C.M.,Michell, B.J.,Cotton, R.G.,Kemp, B.E. (deposition date: 1998-11-11, release date: 1999-04-30, Last modification date: 2024-04-03) |
| Primary citation | Kobe, B.,Jennings, I.G.,House, C.M.,Michell, B.J.,Goodwill, K.E.,Santarsiero, B.D.,Stevens, R.C.,Cotton, R.G.,Kemp, B.E. Structural basis of autoregulation of phenylalanine hydroxylase. Nat.Struct.Biol., 6:442-448, 1999 Cited by PubMed Abstract: Phenylalanine hydroxylase converts phenylalanine to tyrosine, a rate-limiting step in phenylalanine catabolism and protein and neurotransmitter biosynthesis. It is tightly regulated by the substrates phenylalanine and tetrahydrobiopterin and by phosphorylation. We present the crystal structures of dephosphorylated and phosphorylated forms of a dimeric enzyme with catalytic and regulatory properties of the wild-type protein. The structures reveal a catalytic domain flexibly linked to a regulatory domain. The latter consists of an N-terminal autoregulatory sequence (containing Ser 16, which is the site of phosphorylation) that extends over the active site pocket, and an alpha-beta sandwich core that is, unexpectedly, structurally related to both pterin dehydratase and the regulatory domains of metabolic enzymes. Phosphorylation has no major structural effects in the absence of phenylalanine, suggesting that phenylalanine and phosphorylation act in concert to activate the enzyme through a combination of intrasteric and possibly allosteric mechanisms. PubMed: 10331871DOI: 10.1038/8247 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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