| Structural highlights
Function
[GCH1_RAT] May positively regulate nitric oxide synthesis in endothelial cells. May be involved in dopamine synthesis (By similarity). May modify pain sensitivity and persistence.[1] [GFRP_RAT] Mediates tetrahydrobiopterin inhibition of GTP cyclohydrolase 1. This inhibition is reversed by L-phenylalanine.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Crystal structure of the stimulatory complex of GTP cyclohydrolase I and its feedback regulatory protein GFRP.,Maita N, Okada K, Hatakeyama K, Hakoshima T Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1212-7. Epub 2002 Jan 29. PMID:11818540[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tegeder I, Costigan M, Griffin RS, Abele A, Belfer I, Schmidt H, Ehnert C, Nejim J, Marian C, Scholz J, Wu T, Allchorne A, Diatchenko L, Binshtok AM, Goldman D, Adolph J, Sama S, Atlas SJ, Carlezon WA, Parsegian A, Lotsch J, Fillingim RB, Maixner W, Geisslinger G, Max MB, Woolf CJ. GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence. Nat Med. 2006 Nov;12(11):1269-77. Epub 2006 Oct 22. PMID:17057711 doi:10.1038/nm1490
- ↑ Maita N, Okada K, Hatakeyama K, Hakoshima T. Crystal structure of the stimulatory complex of GTP cyclohydrolase I and its feedback regulatory protein GFRP. Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1212-7. Epub 2002 Jan 29. PMID:11818540 doi:10.1073/pnas.022646999
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