1wpl
From Proteopedia
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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 NA, ZN, HBI and 3PO 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
Page seeded by OCA on Wed Nov 21 05:35:03 2007
