1j8u

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[[Image:1j8u.gif|left|200px]]
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==Overview==
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{{ABSTRACT_11718561}}
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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.
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==Disease==
==Disease==
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==About this Structure==
==About this Structure==
1J8U is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The following page contains interesting information on the relation of 1J8U with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb61_1.html Phenylalanine Hydroxylase]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1J8U OCA].
1J8U is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The following page contains interesting information on the relation of 1J8U with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb61_1.html Phenylalanine Hydroxylase]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1J8U OCA].
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==Reference==
 
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High resolution crystal structures of the catalytic domain of human phenylalanine hydroxylase in its catalytically active Fe(II) form and binary complex with tetrahydrobiopterin., Andersen OA, Flatmark T, Hough E, J Mol Biol. 2001 Nov 23;314(2):279-91. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11718561 11718561]
 
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Phenylalanine 4-monooxygenase]]
[[Category: Phenylalanine 4-monooxygenase]]
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[[Category: Ferrous iron]]
[[Category: Ferrous iron]]
[[Category: Tetrahydrobiopterin]]
[[Category: Tetrahydrobiopterin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 20:55:42 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jun 26 17:35:03 2008''

Revision as of 14:35, 26 June 2008

Image:1j8u.png

Template:STRUCTURE 1j8u

Catalytic Domain of Human Phenylalanine Hydroxylase Fe(II) in Complex with Tetrahydrobiopterin


Template:ABSTRACT 11718561

Disease

Known disease associated with this structure: Phenylketonuria OMIM:[261600], Hyperphenylalaninemia, mild OMIM:[261600]

About this Structure

1J8U is a Single protein structure of sequence from Homo sapiens. The following page contains interesting information on the relation of 1J8U with [Phenylalanine Hydroxylase]. Full crystallographic information is available from OCA.

Page seeded by OCA on Thu Jun 26 17:35:03 2008

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