Crystal Structure of the Stimulatory Complex of GTP Cyclohydrolase I and Its Feedback Regulatory Protein GFRP

• Published in: Proceedings of the National Academy of Sciences - PNAS 2002-02, Vol.99 (3), p.1212-1217
• Main Authors: Maita, Nobuo, Okada, Kengo, Hatakeyama, Kazuyuki, Hakoshima, Toshio
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Atoms; Biochemistry; Biological Sciences; Crystal structure; Crystallography, X-Ray; Crystals; Enzyme Inhibitors - chemistry; Enzymes; Escherichia coli - genetics; GTP Cyclohydrolase - antagonists & inhibitors; GTP Cyclohydrolase - chemistry; Hydrogen bonds; Intracellular Signaling Peptides and Proteins; Models, Molecular; Molecular Sequence Data; Molecules; Monomers; Potassium; Protein Conformation; Protein Structure, Secondary; Proteins; Proteins - chemistry; Rats; Recombinant Proteins - chemistry; Sequence Alignment; Sequence Homology, Amino Acid; Zinc
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.022646999

In the presence of phenylalanine, GTP cyclohydrolase I feedback regulatory protein (GFRP) forms a stimulatory 360-kDa complex with GTP cyclohydrolase I (GTPCHI), which is the rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin. The crystal structure of the stimulatory complex reveals that the GTPCHI decamer is sandwiched by two GFRP homopentamers. Each GFRP pentamer forms a symmetrical five-membered ring similar toβ-propeller. Five phenylalanine molecules are buried inside each interface between GFRP and GTPCHI, thus enhancing the binding of these proteins. The complex structure suggests that phenylala nine-induced GTPCHI·GFRP complex formation enhances GTPCHI activity by locking the enzyme in the active state.