Sandbox Reserved 642: Difference between revisions

PheOH can exist as a dimer or tetramer with identical subunits. Each subunit is organized  to have a regulatory, a catalytic and a tetramerization domain. The native form of human PheOH has an estimated secondary structure composed 48% alpha-helices, 28% extended structures, 12% beta-turns, and 12% non-structured conformations. The more structured elements are usually concentrated in the catalytic C-terminal domain of the protein, while the more flexible and unstructured elements are grouped in the regulatory N-terminal domain.<ref> Chehin, R., M. Thorolfsson, PM. Knappskog, A. Martinez, T. Flatmark, JL. Arrondo, and A. Muga,Domain structure and stability of human phenylalanine hydroxylase inferred from infrared spectroscopy[http://www.ncbi.nlm.nih.gov/pubmed/9490012]</ref> The PheOH model protein was generated via x-ray crystallography.<ref> Erlandsen H., DirSci; Marianne G. Patch, PhD; Alejandra Gamez, PhD; Mary Straub; and Raymond C. Stevens, PhD. Structural Studies on Phenylalanine Hydroxylase and Implications Toward Understanding and Treating Phenylketonuria [http://www.pkuworld.org/home/docs/literature/erlandsen_2003_p.pdf]</ref>  

The catalytic domain of phenylalanine hydroxylase includes resides 143-410.  This region has a basket-like arrangement consisting of 13 alpha-helices and 8 beta-strands. This region of the protein also includes the active site.  The active site of PheOH can be found in the center of the catalytic domain and is characterized by a 13 Angstroms deep and 10 Angstroms wide hydrophobic pocket. Lining the active site are 3 glutamates, 2 histadines and 1 tyrosine residue along with hydrophobic residues for a total of 34 amino acids. Covering the entrance of the active site is a short loop consisting or residues 378-381.   

The center of each catalytic domain consists of an iron ion which is vital to the enzyme activity.  The iron atom binds in the active site to  <scene name='Sandbox_Reserved_642/Iron_binding/2'>histadine residues 285 and 290, 1 oxygen atom in glutamate 330</scene>. Histadine 285 and 290 were found to be required for the binding of iron through site directed mutagenisis studies.  The iron ions are coordinated to three water molecules and arrange in an octahedral geometry.  The active site also binds the cofactor tetrahydrobiopterin.  This cofactor binds closely to the iron ion and forma hydrogen bonds with two of the three water molecules.  The cofactor also forms hydrogen bonds with the carbonyl oxygen of the protein residues including Ala322, Gly247, and Leu249 and the amide of Leu249.