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1wpl

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{{STRUCTURE_1wpl| PDB=1wpl | SCENE= }}
{{STRUCTURE_1wpl| PDB=1wpl | SCENE= }}
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'''Crystal structure of the inhibitory form of rat GTP cyclohydrolase I/GFRP complex'''
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===Crystal structure of the inhibitory form of rat GTP cyclohydrolase I/GFRP complex===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 15448133 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15448133}}
==About this Structure==
==About this Structure==
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[[Category: Okada, K.]]
[[Category: Okada, K.]]
[[Category: Enzyme-regulatory protein complex]]
[[Category: Enzyme-regulatory protein complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 13:59:04 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 08:10:11 2008''

Revision as of 05:10, 28 July 2008

Image:1wpl.png

Template:STRUCTURE 1wpl

Crystal structure of the inhibitory form of rat GTP cyclohydrolase I/GFRP complex

Template:ABSTRACT PUBMED 15448133

About this Structure

1WPL is a Protein complex structure of sequences from Rattus norvegicus. 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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