Crystal structure of the stimulatory complex of GTP cyclohydrolase I and its feedback regulatory protein GFRP

AUTOR(ES)

Maita, Nobuo

FONTE

The National Academy of Sciences

RESUMO

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 β-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⋅GFRP complex formation enhances GTPCHI activity by locking the enzyme in the active state.

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