Sandbox Reserved 642: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 17: | Line 17: | ||
'''Tetramerization Domain''' | '''Tetramerization Domain''' | ||
Phenylalanine Hydroxylase exists in equilibrium between a homodimer and a homotetramer. The region responsible for the tertamerization is the <scene name='Sandbox_Reserved_642/Tetramerization_domain/1'>tetramerization domain</scene> located at the C terminal end of the protein. It consists of residues 411-452. The tetramerization domain consists of 2 beta-strands forming a beta-ribbon and an alpha-helix that is 40 angstroms long. The four alpha helices, consisting of one from each monomer, pack into a coil coil motif with the helices arranged in an anti parallel manner.<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> <Structure load='1J8U' size='300' frame='true' align=' | Phenylalanine Hydroxylase exists in equilibrium between a homodimer and a homotetramer. The region responsible for the tertamerization is the <scene name='Sandbox_Reserved_642/Tetramerization_domain/1'>tetramerization domain</scene> located at the C terminal end of the protein. It consists of residues 411-452. The tetramerization domain consists of 2 beta-strands forming a beta-ribbon and an alpha-helix that is 40 angstroms long. The four alpha helices, consisting of one from each monomer, pack into a coil coil motif with the helices arranged in an anti parallel manner.<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> <Structure load='1J8U' size='300' frame='true' align='right' caption='catalytic domain of human phenylalanine hydroxylase in its catalytically active Fe(II) form and binary complex with tetrahydrobiopterin' scene='Insert optional scene name here' /> | ||
'''Regulatory Domain''' | '''Regulatory Domain''' | ||
Housed in the N-terminus, the regulatory domain contains residues 19-142 and is more flexible than the other domains. The core of this domain contains an alpha beta sandwich and a beta alpha beta double motif. <ref> Bostjan Kobe, Ian G. Jennings, Colin M. House1, Belinda J. Michell, Kenneth E. Goodwill, Bernard D. Santarsiero, Raymond C. Stevens, Richard G. H. Cotton and Bruce E. Kemp. Nature Structural Biology 6, 442 - 448 (1999), Structural basis of autoregulation of phenylalanine hydroxylase, [http://http://www.nature.com/nsmb/journal/v6/n5/full/nsb0599_442.html]</ref> | Housed in the N-terminus, the regulatory domain contains residues 19-142 and is more flexible than the other domains. The core of this domain contains an alpha beta sandwich and a beta alpha beta double motif. <ref> Bostjan Kobe, Ian G. Jennings, Colin M. House1, Belinda J. Michell, Kenneth E. Goodwill, Bernard D. Santarsiero, Raymond C. Stevens, Richard G. H. Cotton and Bruce E. Kemp. Nature Structural Biology 6, 442 - 448 (1999), Structural basis of autoregulation of phenylalanine hydroxylase, [http://http://www.nature.com/nsmb/journal/v6/n5/full/nsb0599_442.html]</ref> | ||
== '''Mechanism''' == | == '''Mechanism''' == | ||
Although the exact mechanism of phenylalanine degradation is still not fully understood, the main reaction requires the addition of an hydroxyl group to the benzene ring of the phenylalanine residue. In order for this process to occur, the cofactor tetrahydrobiopterin(BH4) loses two hydrogen atoms to become dihydrobiopterin. BH4 acts as a reductant by reducing one of the diatomic oxygens while the other is added to the 6-membered ring. In order to stabilize the substrate- enzyme complex as this reaction occurs, an iron atom within the protein is necessary. It is within the active site that the hydrogen atom from phenylalanine is stripped off and replaced with a hydroxyl group.<ref> College, Davidson. Phenylalanine Hydroxylase [http://www.bio.davidson.edu/Courses/Molbio/MolStudents/spring2010/Piper/Protein.html] </ref> | Although the exact mechanism of phenylalanine degradation is still not fully understood, the main reaction requires the addition of an hydroxyl group to the benzene ring of the phenylalanine residue. In order for this process to occur, the cofactor tetrahydrobiopterin(BH4) loses two hydrogen atoms to become dihydrobiopterin. BH4 acts as a reductant by reducing one of the diatomic oxygens while the other is added to the 6-membered ring. In order to stabilize the substrate- enzyme complex as this reaction occurs, an iron atom within the protein is necessary. It is within the active site that the hydrogen atom from phenylalanine is stripped off and replaced with a hydroxyl group.<ref> College, Davidson. Phenylalanine Hydroxylase [http://www.bio.davidson.edu/Courses/Molbio/MolStudents/spring2010/Piper/Protein.html] </ref> | ||
[[Image:Phenylalanine_Hydroxylase_mechanism.jpg |thumb|200 px| | [[Image:Phenylalanine_Hydroxylase_mechanism.jpg |thumb|200 px|center|Reaction catalyzed by PheOH]] | ||
