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- Title
Structural insights into the dual substrate specificities of mammalian and Dictyostelium dihydropteridine reductases toward two stereoisomers of quinonoid dihydrobiopterin
- Authors
Chen, Cong; Kim, Hye Lim; Zhuang, Ningning; Seo, Kyung Hye; Park, Ki Hun; Han, Chang-deok; Park, Young Shik; Lee, Kon Ho
- Abstract
Abstract: 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 2.16Å 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±0.4μM) 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)
- Subjects
DICTYOSTELIUM; STEREOISOMERS; MAMMALS; TETRAHYDROBIOPTERIN; CHEMICAL structure; PROTEIN-protein interactions; PROTEIN structure; BINDING sites
- Publication
FEBS Letters, 2011, Vol 585, Issue 17, p2640
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2011.07.018