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PMID:11818540

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Citation

Maita, N, Okada, K, Hatakeyama, K and Hakoshima, T (2002) Crystal structure of the stimulatory complex of GTP cyclohydrolase I and its feedback regulatory protein GFRP. Proc. Natl. Acad. Sci. U.S.A. 99:1212-7

Abstract

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 to beta-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 phenylalanine-induced GTPCHI x GFRP complex formation enhances GTPCHI activity by locking the enzyme in the active state.

Links

PubMed PMC122169 Online version:10.1073/pnas.022646999

Keywords

Amino Acid Sequence; Animals; Crystallography, X-Ray; Enzyme Inhibitors/chemistry; Escherichia coli/genetics; GTP Cyclohydrolase/antagonists & inhibitors; GTP Cyclohydrolase/chemistry; Models, Molecular; Molecular Sequence Data; Protein Conformation; Protein Structure, Secondary; Proteins/chemistry; Rats; Recombinant Proteins/chemistry; Sequence Alignment; Sequence Homology, Amino Acid

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