1j8t
From Proteopedia
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|PDB= 1j8t |SIZE=350|CAPTION= <scene name='initialview01'>1j8t</scene>, resolution 1.7Å | |PDB= 1j8t |SIZE=350|CAPTION= <scene name='initialview01'>1j8t</scene>, resolution 1.7Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=FE2:FE (II) ION'>FE2</scene> | + | |LIGAND= <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Phenylalanine_4-monooxygenase Phenylalanine 4-monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.16.1 1.14.16.1] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Phenylalanine_4-monooxygenase Phenylalanine 4-monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.16.1 1.14.16.1] </span> |
|GENE= PAH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= PAH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1j8u|1J8U]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1j8t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j8t OCA], [http://www.ebi.ac.uk/pdbsum/1j8t PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1j8t RCSB]</span> | ||
}} | }} | ||
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==Disease== | ==Disease== | ||
| - | Known | + | Known disease associated with this structure: Phenylketonuria OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=261600 261600]], Hyperphenylalaninemia, mild OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=261600 261600]] |
==About this Structure== | ==About this Structure== | ||
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[[Category: Flatmark, T.]] | [[Category: Flatmark, T.]] | ||
[[Category: Hough, E.]] | [[Category: Hough, E.]] | ||
| - | [[Category: FE2]] | ||
[[Category: 2-his-1-carboxylate facial triad]] | [[Category: 2-his-1-carboxylate facial triad]] | ||
[[Category: ferrous iron]] | [[Category: ferrous iron]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:30:13 2008'' |
Revision as of 18:30, 30 March 2008
| |||||||
| , resolution 1.7Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | PAH (Homo sapiens) | ||||||
| Activity: | Phenylalanine 4-monooxygenase, with EC number 1.14.16.1 | ||||||
| Related: | 1J8U
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Catalytic Domain of Human Phenylalanine Hydroxylase Fe(II)
Contents |
Overview
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.
Disease
Known disease associated with this structure: Phenylketonuria OMIM:[261600], Hyperphenylalaninemia, mild OMIM:[261600]
About this Structure
1J8T is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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:11718561
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