Crystal structure of rat GTP cyclohydrolase I feedback regulatory protein, GFRP.
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.
Bader
G
G
Abteilung Strukturforschung, Max-Planck-Institut für Biochemie, Am Klopferspitz 18a, Martinsried, D-82152, Germany.
Schiffmann
S
S
Herrmann
A
A
Fischer
M
M
Gütlich
M
M
Auerbach
G
G
Ploom
T
T
Bacher
A
A
Huber
R
R
Lemm
T
T
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
C101092:GCHFR protein, human; C491065:Gchfr protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D006136:GTP Cyclohydrolase