title: Crystal structure of rat GTP cyclohydrolase I feedback regulatory protein, GFRP.
abstract: Tetrahydrobiopterin, the cofactor required for hydroxylation of aromatic amino acids regulates its own synthesis in mammals through feedback inhibition of GTP cyclohydrolase I. This mechanism is mediated by a regulatory subunit called GTP cyclohydrolase I feedback regulatory protein (GFRP). The 2.6 A resolution crystal structure of rat GFRP shows that the protein forms a pentamer. This indicates a model for the interaction of mammalian GTP cyclohydrolase I with its regulator, GFRP. Kinetic investigations of human GTP cyclohydrolase I in complex with rat and human GFRP showed similar regulatory effects of both GFRP proteins.
authors.affiliation: Abteilung Strukturforschung, Max-Planck-Institut für Biochemie, Am Klopferspitz 18a, Martinsried, D-82152, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Bader
authors.forename: S
authors.initials: S
authors.lastname: Schiffmann
authors.forename: A
authors.initials: A
authors.lastname: Herrmann
authors.forename: M
authors.initials: M
authors.lastname: Fischer
authors.forename: M
authors.initials: M
authors.lastname: Gütlich
authors.forename: G
authors.initials: G
authors.lastname: Auerbach
authors.forename: T
authors.initials: T
authors.lastname: Ploom
authors.forename: A
authors.initials: A
authors.lastname: Bacher
authors.forename: R
authors.initials: R
authors.lastname: Huber
authors.forename: T
authors.initials: T
authors.lastname: Lemm
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D005246:Feedback; D006136:GTP Cyclohydrolase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats; D016415:Sequence Alignment; D055672:Static Electricity
chemical_list: C101092:GCHFR protein, human; C491065:Gchfr protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D006136:GTP Cyclohydrolase