1WPL
Crystal structure of the inhibitory form of rat GTP cyclohydrolase I/GFRP complex
Summary for 1WPL
| Entry DOI | 10.2210/pdb1wpl/pdb |
| Related | 1is7 |
| Descriptor | GTP cyclohydrolase I, GTP cyclohydrolase I feedback regulatory protein, ZINC ION, ... (7 entities in total) |
| Functional Keywords | enzyme-regulatory protein complex, hydrolase-protein binding complex, hydrolase/protein binding |
| Biological source | Rattus norvegicus (Norway rat) More |
| Cellular location | Cytoplasm (By similarity): P22288 Nucleus (By similarity): P70552 |
| Total number of polymer chains | 20 |
| Total formula weight | 360884.82 |
| Authors | Maita, N.,Hatakeyama, K.,Okada, K.,Hakoshima, T. (deposition date: 2004-09-08, release date: 2004-09-28, Last modification date: 2023-10-25) |
| Primary citation | 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 Cited by 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: 15448133DOI: 10.1074/jbc.M409440200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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