【文章名】Structural insights into the dual substrate specificities of mammalian and Dictyostelium dihydropteridine reductases toward two stereoisomers of quinonoid dihydrobiopterin
Structural insights into the dual substrate specificities of mammalian and Dictyostelium dihydropteridine reductases toward two stereoisomers of quinonoid dihydrobiopterin
作者
Chen, C; Kim, HL; Zhuang, NN; Seo, KH; Park, KH; Han, CD; Park, YS; Lee, KH
[摘要]:Up to now, D-threo-tetrahydrobiopterin (DH4, dictyopterin) was detected only in Dictyostelium discoideum, while the isomer L-erythro-tetrahydrobioterin (BH4) is common in mammals. To elucidate the mechanism of DH4 regeneration by D. discoideum dihydropteridine reductase (DicDHPR), we have determined the crystal structure of DicDHPR complexed with NAD(+) at 2.16 angstrom resolution. Significant structural differences from mammalian DHPRs are found around the coenzyme binding site, resulting in a higher K-m value for NADH (K-m = 46.51 +/- 0.4 mu M) than mammals. In addition, we have found that rat DHPR as well as DicDHPR could bind to both substrates quinonoid-BH2 and quinonoid-DH2 by docking calculations and have confirmed their catalytic activity by in vitro assay. Structured summary of protein interactions: DHPR binds to DHPR by X-ray crystallography (View interaction) (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.