1WPL

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

1WPL の概要

• エントリーDOI: 10.2210/pdb1wpl/pdb
• 関連するPDBエントリー: 1is7
• 分子名称: GTP cyclohydrolase I, GTP cyclohydrolase I feedback regulatory protein, ZINC ION, ... (7 entities in total)
• 機能のキーワード: enzyme-regulatory protein complex, hydrolase-protein binding complex, hydrolase/protein binding
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• 細胞内の位置: Cytoplasm (By similarity): P22288; Nucleus (By similarity): P70552
• タンパク質・核酸の鎖数: 20
• 化学式量合計: 360884.82

構造登録者

Maita, N.,Hatakeyama, K.,Okada, K.,Hakoshima, T. (登録日: 2004-09-08, 公開日: 2004-09-28, 最終更新日: 2023-10-25)

主引用文献

Maita, N.,Hatakeyama, K.,Okada, K.,Hakoshima, T.
Structural basis of biopterin-induced inhibition of GTP cyclohydrolase I by GFRP, its feedback regulatory protein
J.Biol.Chem., 279:51534-51540, 2004

PubMed Abstract: 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.

PubMed: 15448133
DOI: 10.1074/jbc.M409440200

実験手法

X-RAY DIFFRACTION (2.8 Å)