2pah

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
{{STRUCTURE_2pah| PDB=2pah | SCENE= }}
+
==TETRAMERIC HUMAN PHENYLALANINE HYDROXYLASE==
-
===TETRAMERIC HUMAN PHENYLALANINE HYDROXYLASE===
+
<StructureSection load='2pah' size='340' side='right' caption='[[2pah]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
-
{{ABSTRACT_PUBMED_9642259}}
+
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[2pah]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The January 2005 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Phenylalanine Hydroxylase'' by Shuchismita Dutta and David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2005_1 10.2210/rcsb_pdb/mom_2005_1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PAH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2PAH FirstGlance]. <br>
 +
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene><br>
 +
<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2pah FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pah OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2pah RCSB], [http://www.ebi.ac.uk/pdbsum/2pah 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==
+
== Evolutionary Conservation ==
-
[[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>
+
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pa/2pah_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Phenylalanine hydroxylase (PheOH) catalyzes the conversion of L-phenylalanine to L-tyrosine, the rate-limiting step in the oxidative degradation of phenylalanine. Mutations in the human PheOH gene cause phenylketonuria, a common autosomal recessive metabolic disorder that in untreated patients often results in varying degrees of mental retardation. We have determined the crystal structure of human PheOH (residues 118-452). The enzyme crystallizes as a tetramer with each monomer consisting of a catalytic and a tetramerization domain. The tetramerization domain is characterized by the presence of a domain swapping arm that interacts with the other monomers forming an antiparallel coiled-coil. The structure is the first report of a tetrameric PheOH and displays an overall architecture similar to that of the functionally related tyrosine hydroxylase. In contrast to the tyrosine hydroxylase tetramer structure, a very pronounced asymmetry is observed in the phenylalanine hydroxylase, caused by the occurrence of two alternate conformations in the hinge region that leads to the coiled-coil helix. Examination of the mutations causing PKU shows that some of the most frequent mutations are located at the interface of the catalytic and tetramerization domains. Their effects on the structural and cellular stability of the enzyme are discussed.
-
==About this Structure==
+
Structure of tetrameric human phenylalanine hydroxylase and its implications for phenylketonuria.,Fusetti F, Erlandsen H, Flatmark T, Stevens RC J Biol Chem. 1998 Jul 3;273(27):16962-7. PMID:9642259<ref>PMID:9642259</ref>
-
[[2pah]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The January 2005 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Phenylalanine Hydroxylase'' by Shuchismita Dutta and David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2005_1 10.2210/rcsb_pdb/mom_2005_1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PAH 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:009642259</ref><references group="xtra"/><references/>
+
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Phenylalanine 4-monooxygenase]]
[[Category: Phenylalanine 4-monooxygenase]]

Revision as of 19:22, 30 September 2014

TETRAMERIC HUMAN PHENYLALANINE HYDROXYLASE

2pah, resolution 3.10Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2pah"
Views
Personal tools
Navigation
Toolbox