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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 |
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creator | Maita, Nobuo Okada, Kengo Hatakeyama, Kazuyuki Hakoshima, Toshio |
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. |
doi_str_mv | 10.1073/pnas.022646999 |
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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.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>11818540</pmid><doi>10.1073/pnas.022646999</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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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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