PDBsum entry: 1j8t

Oxidoreductase

PDB id: 1j8t

Contents

Protein chain

307 a.a. *

Metals

FE2

Waters ×278

* Residue conservation analysis

PDB id:

1j8t

Name:

Oxidoreductase

Title:

Catalytic domain of human phenylalanine hydroxylase fe(ii)

Structure:

Phenylalanine-4-hydroxylase. Chain: a. Fragment: catalytic domain (residues 103-427). Synonym: phe-4-monooxygenase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pah. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.70Å R-factor: 0.197 R-free: 0.252

Authors:

O.A.Andersen,T.Flatmark,E.Hough

Key ref:

O.A.Andersen et al. (2001). 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, 279-291. PubMed id: 11718561 DOI: 10.1006/jmbi.2001.5061

Date:

22-May-01 Release date: 22-May-02

Protein chain

P00439  (PH4H_HUMAN) -  Phenylalanine-4-hydroxylase

Seq: 452 a.a.

Struc: 307 a.a.

Enzyme reactions

• Enzyme class: E.C.1.14.16.1 - Phenylalanine 4-monooxygenase.
• Pathway: Phenylalanine and Tyrosine Biosynthesis
• Reaction: L-phenylalanine + tetrahydrobiopterin + O₂ = L-tyrosine + 4a-hydroxytetrahydrobiopterin
• Cofactor: Iron

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Biological process: oxidation reduction (2 terms)
• Biochemical function: monooxygenase activity (3 terms)

reference

DOI no: 10.1006/jmbi.2001.5061

J Mol Biol 314:279-291 (2001)

PubMed id: 11718561

High resolution crystal structures of the catalytic domain of human phenylalanine hydroxylase in its catalytically active Fe(II) form and binary complex with tetrahydrobiopterin.

O.A.Andersen, T.Flatmark, E.Hough.

ABSTRACT

The crystal structures of the catalytic domain (DeltaN1-102/DeltaC428-452) of human phenylalanine hydroxylase (hPheOH) in its catalytically competent Fe(II) form and binary complex with the reduced pterin cofactor 6(R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) have been determined to 1.7 and 1.5 A, respectively. When compared with the structures reported for various catalytically inactive Fe(III) forms, several important differences have been observed, notably at the active site. Thus, the non-liganded hPheOH-Fe(II) structure revealed well defined electron density for only one of the three water molecules reported to be coordinated to the iron in the high-spin Fe(III) form, as well as poor electron density for parts of the coordinating side-chain of Glu330. The reduced cofactor (BH4), which adopts the expected half-semi chair conformation, is bound in the second coordination sphere of the catalytic iron with a C4a-iron distance of 5.9 A. BH4 binds at the same site as L-erythro-7,8-dihydrobiopterin (BH2) in the binary hPheOH-Fe(III)-BH2 complex forming an aromatic pi-stacking interaction with Phe254 and a network of hydrogen bonds. However, compared to that structure the pterin ring is displaced about 0.5 A and rotated about 10 degrees, and the torsion angle between the hydroxyl groups of the cofactor in the dihydroxypropyl side-chain has changed by approximately 120 degrees enabling O2' to make a strong hydrogen bond (2.4 A) with the side-chain oxygen of Ser251. Carbon atoms in the dihydroxypropyl side-chain make several hydrophobic contacts with the protein. The iron is six-coordinated in the binary complex, but the overall coordination geometry is slightly different from that of the Fe(III) form. Most important was the finding that the binding of BH4 causes the Glu330 ligand to change its coordination to the iron when comparing with non-liganded hPheOH-Fe(III) and the binary hPheOH-Fe(III)-BH2 complex.

Selected figure(s)

Figure 4.
Figure 4. Schematic diagram of BH[4]-protein interactions. The BH[4] molecule is shown with purple bonds, nitrogen atoms are blue, oxygen atoms red, water oxygens green, carbon atoms black and the iron is yellow. The Figure was produced using LIGPLOT21, and edited using CorelDRAW 9.0.

Figure 5.
Figure 5. Top (a) and side (b) view of the electron density of tetrahydrobiopterin contoured as 2F[o] -F[c] maps at 1.7 s showing that all atoms are well defined. The non-planarity of the pyrazine ring can clearly be identified in (b). The Figure was produced using BOBSCRIPT20.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2001, 314, 279-291) copyright 2001.

Figures were selected by an automated process.