View source for 1wpl


==Crystal structure of the inhibitory form of rat GTP cyclohydrolase I/GFRP complex==
<StructureSection load='1wpl' size='340' side='right'caption='[[1wpl]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1wpl]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WPL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WPL FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3PO:TRIPHOSPHATE'>3PO</scene>, <scene name='pdbligand=HBI:7,8-DIHYDROBIOPTERIN'>HBI</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1wpl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wpl OCA], [https://pdbe.org/1wpl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wpl RCSB], [https://www.ebi.ac.uk/pdbsum/1wpl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wpl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GCH1_RAT GCH1_RAT] May positively regulate nitric oxide synthesis in endothelial cells. May be involved in dopamine synthesis (By similarity). May modify pain sensitivity and persistence.<ref>PMID:17057711</ref> 
== Evolutionary Conservation ==
[[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/wp/1wpl_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/main_output.php?pdb_ID=1wpl ConSurf].
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== Publication Abstract from PubMed ==
GTP cyclohydrolase I (GTPCHI) is the rate-limiting enzyme involved in the biosynthesis of tetrahydrobiopterin, a key cofactor necessary for nitric oxide synthase and for the hydroxylases that are involved in the production of catecholamines and serotonin. In animals, the GTPCHI feedback regulatory protein (GFRP) binds GTPCHI to mediate feed-forward activation of GTPCHI activity in the presence of phenylalanine, whereas it induces feedback inhibition of enzyme activity in the presence of biopterin. Here, we have reported the crystal structure of the biopterin-induced inhibitory complex of GTPCHI and GFRP and compared it with the previously reported phenylalanine-induced stimulatory complex. The structure reveals five biopterin molecules located at each interface between GTPCHI and GFRP. Induced fitting structural changes by the biopterin binding expand large conformational changes in GTPCHI peptide segments forming the active site, resulting in inhibition of the activity. By locating 3,4-dihydroxy-phenylalanine-responsive dystonia mutations in the complex structure, we found mutations that may possibly disturb the GFRP-mediated regulation of GTPCHI.

Structural basis of biopterin-induced inhibition of GTP cyclohydrolase I by GFRP, its feedback regulatory protein.,Maita N, Hatakeyama K, Okada K, Hakoshima T J Biol Chem. 2004 Dec 3;279(49):51534-40. Epub 2004 Sep 23. PMID:15448133<ref>PMID:15448133</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1wpl" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cyclohydrolase 3D structures|Cyclohydrolase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Hakoshima T]]
[[Category: Hatakeyama K]]
[[Category: Maita N]]
[[Category: Okada K]]