1wpl
From Proteopedia
(New page: 200px<br /><applet load="1wpl" size="450" color="white" frame="true" align="right" spinBox="true" caption="1wpl, resolution 2.8Å" /> '''Crystal structure of ...) |
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| - | [[Image:1wpl.gif|left|200px]]<br /><applet load="1wpl" size=" | + | [[Image:1wpl.gif|left|200px]]<br /><applet load="1wpl" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1wpl, resolution 2.8Å" /> | caption="1wpl, resolution 2.8Å" /> | ||
'''Crystal structure of the inhibitory form of rat GTP cyclohydrolase I/GFRP complex'''<br /> | '''Crystal structure of the inhibitory form of rat GTP cyclohydrolase I/GFRP complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | GTP cyclohydrolase I (GTPCHI) is the rate-limiting enzyme involved in the | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1WPL is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with NA, ZN, HBI and 3PO as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/GTP_cyclohydrolase_I GTP cyclohydrolase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.16 3.5.4.16] Full crystallographic information is available from [http:// | + | 1WPL is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=NA:'>NA</scene>, <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=HBI:'>HBI</scene> and <scene name='pdbligand=3PO:'>3PO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/GTP_cyclohydrolase_I GTP cyclohydrolase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.16 3.5.4.16] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WPL OCA]. |
==Reference== | ==Reference== | ||
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[[Category: enzyme-regulatory protein complex]] | [[Category: enzyme-regulatory protein complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:46:50 2008'' |
Revision as of 13:46, 21 February 2008
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Crystal structure of the inhibitory form of rat GTP cyclohydrolase I/GFRP complex
Overview
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.
About this Structure
1WPL is a Protein complex structure of sequences from Rattus norvegicus with , , and as ligands. Active as GTP cyclohydrolase I, with EC number 3.5.4.16 Full crystallographic information is available from OCA.
Reference
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
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