鸟苷三磷酸环化水解酶I与其反馈调节蛋白GFRP的刺激复合物的晶体结构。
Crystal structure of the stimulatory complex of GTP cyclohydrolase I and its feedback regulatory protein GFRP.
作者信息
Maita Nobuo, Okada Kengo, Hatakeyama Kazuyuki, Hakoshima Toshio
机构信息
Department of Molecular Biology, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0101, Japan.
出版信息
Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1212-7. doi: 10.1073/pnas.022646999. Epub 2002 Jan 29.
Abstract
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.
摘要
在苯丙氨酸存在的情况下，GTP环化水解酶I反馈调节蛋白（GFRP）与GTP环化水解酶I（GTPCHI）形成一个具有刺激作用的360 kDa复合物，GTPCHI是四氢生物蝶呤生物合成中的限速酶。该刺激复合物的晶体结构显示，GTPCHI十聚体被两个GFRP同五聚体夹在中间。每个GFRP五聚体形成一个类似于β-螺旋桨的对称五元环。五个苯丙氨酸分子埋藏在每个GFRP与GTPCHI之间的界面内，从而增强了这些蛋白质的结合。该复合物结构表明，苯丙氨酸诱导的GTPCHI x GFRP复合物形成通过将酶锁定在活性状态来增强GTPCHI活性。
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