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

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 tha...

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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
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cited_by cdi_FETCH-LOGICAL-c486t-6c909348c87730ff6d8e5dd1fe4b246fa2dfb6725628ec1aaf76c0c59e7abf713
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container_title Proceedings of the National Academy of Sciences - PNAS
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creator Maita, Nobuo
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description 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.
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source Open Access: PubMed Central; JSTOR Archival Journals and Primary Sources Collection
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
title Crystal Structure of the Stimulatory Complex of GTP Cyclohydrolase I and Its Feedback Regulatory Protein GFRP
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