1mmk: Difference between revisions
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[[Image:1mmk.gif|left|200px]] | [[Image:1mmk.gif|left|200px]] | ||
'''Crystal structure of ternary complex of the catalytic domain of human phenylalanine hydroxylase ((FeII)) complexed with tetrahydrobiopterin and thienylalanine''' | {{Structure | ||
|PDB= 1mmk |SIZE=350|CAPTION= <scene name='initialview01'>1mmk</scene>, resolution 2.0Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene> and <scene name='pdbligand=TIH:BETA(2-THIENYL)ALANINE'>TIH</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] | |||
|GENE= PAH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''Crystal structure of ternary complex of the catalytic domain of human phenylalanine hydroxylase ((FeII)) complexed with tetrahydrobiopterin and thienylalanine''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1MMK is a [ | 1MMK is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MMK OCA]. | ||
==Reference== | ==Reference== | ||
2.0A resolution crystal structures of the ternary complexes of human phenylalanine hydroxylase catalytic domain with tetrahydrobiopterin and 3-(2-thienyl)-L-alanine or L-norleucine: substrate specificity and molecular motions related to substrate binding., Andersen OA, Stokka AJ, Flatmark T, Hough E, J Mol Biol. 2003 Oct 31;333(4):747-57. PMID:[http:// | 2.0A resolution crystal structures of the ternary complexes of human phenylalanine hydroxylase catalytic domain with tetrahydrobiopterin and 3-(2-thienyl)-L-alanine or L-norleucine: substrate specificity and molecular motions related to substrate binding., Andersen OA, Stokka AJ, Flatmark T, Hough E, J Mol Biol. 2003 Oct 31;333(4):747-57. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14568534 14568534] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Phenylalanine 4-monooxygenase]] | [[Category: Phenylalanine 4-monooxygenase]] | ||
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[[Category: SO4]] | [[Category: SO4]] | ||
[[Category: TIH]] | [[Category: TIH]] | ||
[[Category: 13 alpha- | [[Category: 13 alpha-helice]] | ||
[[Category: 8 beta- | [[Category: 8 beta-strand]] | ||
[[Category: basket-arrangement]] | [[Category: basket-arrangement]] | ||
[[Category: ferrous iron]] | [[Category: ferrous iron]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:45:21 2008'' | ||
Revision as of 13:45, 20 March 2008
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| , resolution 2.0Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , and | ||||||
| Gene: | PAH (Homo sapiens) | ||||||
| Activity: | Phenylalanine 4-monooxygenase, with EC number 1.14.16.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of ternary complex of the catalytic domain of human phenylalanine hydroxylase ((FeII)) complexed with tetrahydrobiopterin and thienylalanine
OverviewOverview
The crystal structures of the catalytic domain of human phenylalanine hydroxylase (hPheOH) in complex with the physiological cofactor 6(R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH(4)) and the substrate analogues 3-(2-thienyl)-L-alanine (THA) or L-norleucine (NLE) have been determined at 2.0A resolution. The ternary THA complex confirms a previous 2.5A structure, and the ternary NLE complex shows that similar large conformational changes occur on binding of NLE as those observed for THA. Both structures demonstrate that substrate binding triggers structural changes throughout the entire protomer, including the displacement of Tyr138 from a surface position to a buried position at the active site, with a maximum displacement of 20.7A for its hydroxyl group. Two hinge-bending regions, centred at Leu197 and Asn223, act in consort upon substrate binding to create further large structural changes for parts of the C terminus. Thus, THA/L-Phe binding to the active site is likely to represent the epicentre of the global conformational changes observed in the full-length tetrameric enzyme. The carboxyl and amino groups of THA and NLE are positioned identically in the two structures, supporting the conclusion that these groups are of key importance in substrate binding, thus explaining the broad non-physiological substrate specificity observed for artificially activated forms of the enzyme. However, the specific activity with NLE as the substrate was only about 5% of that with THA, which is explained by the different affinities of binding and different catalytic turnover.
DiseaseDisease
Known diseases associated with this structure: Hyperphenylalaninemia, mild OMIM:[261600], Phenylketonuria OMIM:[261600]
About this StructureAbout this Structure
1MMK is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
2.0A resolution crystal structures of the ternary complexes of human phenylalanine hydroxylase catalytic domain with tetrahydrobiopterin and 3-(2-thienyl)-L-alanine or L-norleucine: substrate specificity and molecular motions related to substrate binding., Andersen OA, Stokka AJ, Flatmark T, Hough E, J Mol Biol. 2003 Oct 31;333(4):747-57. PMID:14568534
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