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{{STRUCTURE_4anp|  PDB=4anp  |  SCENE=  }}
==Crystal structure of human phenylalanine hydroxylase in complex with a pharmacological chaperone==
===Crystal structure of human phenylalanine hydroxylase in complex with a pharmacological chaperone===
<StructureSection load='4anp' size='340' side='right' caption='[[4anp]], [[Resolution|resolution]] 2.11&Aring;' scene=''>
{{ABSTRACT_PUBMED_22549968}}
== Structural highlights ==
<table><tr><td colspan='2'>[[4anp]] is a 1 chain structure with 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=4ANP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ANP FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3QI:5,6-DIMETHYL-3-(4-METHYL-2-PYRIDINYL)-2-THIOXO-2,3-DIHYDROTHIENO[2,3-+D]PYRIMIDIN-4(1H)-ONE'>3QI</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1dmw|1dmw]], [[1j8t|1j8t]], [[1j8u|1j8u]], [[1kw0|1kw0]], [[1lrm|1lrm]], [[1mmk|1mmk]], [[1mmt|1mmt]], [[1pah|1pah]], [[1tdw|1tdw]], [[1tg2|1tg2]], [[2pah|2pah]], [[3pah|3pah]], [[4pah|4pah]], [[5pah|5pah]], [[6pah|6pah]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4anp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4anp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4anp RCSB], [http://www.ebi.ac.uk/pdbsum/4anp PDBsum]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/PH4H_HUMAN PH4H_HUMAN]] Defects in PAH are the cause of phenylketonuria (PKU) [MIM:[http://omim.org/entry/261600 261600]]. PKU is an autosomal recessive inborn error of phenylalanine metabolism, due to severe phenylalanine hydroxylase deficiency. It is characterized by blood concentrations of phenylalanine persistently above 1200 mumol (normal concentration 100 mumol) which usually causes mental retardation (unless low phenylalanine diet is introduced early in life). They tend to have light pigmentation, rashes similar to eczema, epilepsy, extreme hyperactivity, psychotic states and an unpleasant 'mousy' odor.<ref>PMID:8594560</ref> <ref>PMID:2840952</ref> <ref>PMID:2564729</ref> <ref>PMID:2615649</ref> <ref>PMID:1975559</ref> <ref>PMID:1671810</ref> <ref>PMID:2014802</ref> <ref>PMID:1672294</ref> <ref>PMID:1672290</ref> <ref>PMID:1679030</ref> <ref>PMID:1709636</ref> <ref>PMID:1355066</ref> <ref>PMID:1363837</ref> <ref>PMID:1363838</ref> <ref>PMID:8406445</ref> <ref>PMID:8068076</ref> <ref>PMID:7833954</ref> <ref>PMID:8889583</ref> <ref>PMID:8889590</ref> <ref>PMID:9048935</ref> <ref>PMID:9101291</ref> <ref>PMID:9521426</ref> <ref>PMID:9600453</ref> <ref>PMID:10200057</ref> <ref>PMID:9452061</ref> <ref>PMID:9452062</ref> <ref>PMID:9792407</ref> <ref>PMID:9792411</ref> <ref>PMID:9950317</ref> <ref>PMID:10679941</ref> <ref>PMID:11326337</ref> <ref>PMID:11180595</ref> <ref>PMID:11385716</ref> <ref>PMID:11461196</ref> <ref>PMID:12501224</ref> <ref>PMID:18538294</ref> <ref>PMID:22526846</ref> <ref>PMID:22513348</ref>  Defects in PAH are the cause of non-phenylketonuria hyperphenylalaninemia (Non-PKU HPA) [MIM:[http://omim.org/entry/261600 261600]]. Non-PKU HPA is a mild form of phenylalanine hydroxylase deficiency characterized by phenylalanine levels persistently below 600 mumol, which allows normal intellectual and behavioral development without treatment. Non-PKU HPA is usually caused by the combined effect of a mild hyperphenylalaninemia mutation and a severe one.  Defects in PAH are the cause of hyperphenylalaninemia (HPA) [MIM:[http://omim.org/entry/261600 261600]]. HPA is the mildest form of phenylalanine hydroxylase deficiency.<ref>PMID:9521426</ref> <ref>PMID:11385716</ref> <ref>PMID:12501224</ref> <ref>PMID:1358789</ref> <ref>PMID:8098245</ref> <ref>PMID:8088845</ref> <ref>PMID:9852673</ref> <ref>PMID:11935335</ref> 
== Function ==


==Disease==
<div style="background-color:#fffaf0;">
[[http://www.uniprot.org/uniprot/PH4H_HUMAN PH4H_HUMAN]] Defects in PAH are the cause of phenylketonuria (PKU) [MIM:[http://omim.org/entry/261600 261600]]. PKU is an autosomal recessive inborn error of phenylalanine metabolism, due to severe phenylalanine hydroxylase deficiency. It is characterized by blood concentrations of phenylalanine persistently above 1200 mumol (normal concentration 100 mumol) which usually causes mental retardation (unless low phenylalanine diet is introduced early in life). They tend to have light pigmentation, rashes similar to eczema, epilepsy, extreme hyperactivity, psychotic states and an unpleasant 'mousy' odor.<ref>PMID:8594560</ref><ref>PMID:2840952</ref><ref>PMID:2564729</ref><ref>PMID:2615649</ref><ref>PMID:1975559</ref><ref>PMID:1671810</ref><ref>PMID:2014802</ref><ref>PMID:1672294</ref><ref>PMID:1672290</ref><ref>PMID:1679030</ref><ref>PMID:1709636</ref><ref>PMID:1355066</ref><ref>PMID:1363837</ref><ref>PMID:1363838</ref><ref>PMID:8406445</ref><ref>PMID:8068076</ref><ref>PMID:7833954</ref><ref>PMID:8889583</ref><ref>PMID:8889590</ref><ref>PMID:9048935</ref><ref>PMID:9101291</ref><ref>PMID:9521426</ref><ref>PMID:9600453</ref><ref>PMID:10200057</ref><ref>PMID:9452061</ref><ref>PMID:9452062</ref><ref>PMID:9792407</ref><ref>PMID:9792411</ref><ref>PMID:9950317</ref><ref>PMID:10679941</ref><ref>PMID:11326337</ref><ref>PMID:11180595</ref><ref>PMID:11385716</ref><ref>PMID:11461196</ref><ref>PMID:12501224</ref><ref>PMID:18538294</ref><ref>PMID:22526846</ref><ref>PMID:22513348</ref>  Defects in PAH are the cause of non-phenylketonuria hyperphenylalaninemia (Non-PKU HPA) [MIM:[http://omim.org/entry/261600 261600]]. Non-PKU HPA is a mild form of phenylalanine hydroxylase deficiency characterized by phenylalanine levels persistently below 600 mumol, which allows normal intellectual and behavioral development without treatment. Non-PKU HPA is usually caused by the combined effect of a mild hyperphenylalaninemia mutation and a severe one.  Defects in PAH are the cause of hyperphenylalaninemia (HPA) [MIM:[http://omim.org/entry/261600 261600]]. HPA is the mildest form of phenylalanine hydroxylase deficiency.<ref>PMID:9521426</ref><ref>PMID:11385716</ref><ref>PMID:12501224</ref><ref>PMID:1358789</ref><ref>PMID:8098245</ref><ref>PMID:8088845</ref><ref>PMID:9852673</ref><ref>PMID:11935335</ref>
== Publication Abstract from PubMed ==
Not without a chaperone: Pharmacological chaperones are designed to bind and ideally stabilise their target protein. Here, we elucidate the molecular mechanism of a potential pharmacological chaperone to treat phenylketonuria. The crystal structure of human phenylalanine hydroxylase with compound IV may help in the rational design of more efficient compounds to treat this disease.


==About this Structure==
Structural and Mechanistic Basis of the Interaction between a Pharmacological Chaperone and Human Phenylalanine Hydroxylase.,Torreblanca R, Lira-Navarrete E, Sancho J, Hurtado-Guerrero R Chembiochem. 2012 Jun 18;13(9):1266-9. doi: 10.1002/cbic.201200188. Epub 2012 Apr, 30. PMID:22549968<ref>PMID:22549968</ref>
[[4anp]] is a 1 chain structure with 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=4ANP OCA].
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>


==See Also==
==See Also==
*[[Phenylalanine hydroxylase|Phenylalanine hydroxylase]]
*[[Phenylalanine hydroxylase|Phenylalanine hydroxylase]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:022549968</ref><references group="xtra"/><references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Phenylalanine 4-monooxygenase]]
[[Category: Phenylalanine 4-monooxygenase]]
[[Category: Hurtado-Guerrero, R.]]
[[Category: Hurtado-Guerrero, R]]
[[Category: Lira-Navarrete, E.]]
[[Category: Lira-Navarrete, E]]
[[Category: Sancho, J.]]
[[Category: Sancho, J]]
[[Category: Torreblanca, R.]]
[[Category: Torreblanca, R]]
[[Category: Folding mechanism]]
[[Category: Folding mechanism]]
[[Category: Oxidoreductase]]
[[Category: Oxidoreductase]]
[[Category: Phenylketonuria]]
[[Category: Phenylketonuria]]
Retrieved from "https://proteopedia.org/4anp"