大鼠GTP环化水解酶I反馈调节蛋白（GFRP）的晶体结构

Crystal structure of rat GTP cyclohydrolase I feedback regulatory protein, GFRP.

作者信息

Bader G, Schiffmann S, Herrmann A, Fischer M, Gütlich M, Auerbach G, Ploom T, Bacher A, Huber R, Lemm T

机构信息

Abteilung Strukturforschung, Max-Planck-Institut für Biochemie, Am Klopferspitz 18a, Martinsried, D-82152, Germany.

出版信息

J Mol Biol. 2001 Oct 5;312(5):1051-7. doi: 10.1006/jmbi.2001.5011.

DOI:10.1006/jmbi.2001.5011

PMID:11580249

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.

摘要

四氢生物蝶呤是芳香族氨基酸羟化所需的辅因子，在哺乳动物中，它通过对鸟苷三磷酸环化水解酶I的反馈抑制来调节自身的合成。该机制由一种名为鸟苷三磷酸环化水解酶I反馈调节蛋白（GFRP）的调节亚基介导。大鼠GFRP的2.6埃分辨率晶体结构表明，该蛋白形成五聚体。这为哺乳动物鸟苷三磷酸环化水解酶I与其调节因子GFRP的相互作用提供了一个模型。对与大鼠和人GFRP复合的人鸟苷三磷酸环化水解酶I的动力学研究表明，两种GFRP蛋白具有相似的调节作用。