title: Structural insights into the dual substrate specificities of mammalian and Dictyostelium dihydropteridine reductases toward two stereoisomers of quinonoid dihydrobiopterin.
abstract: Up to now, d-threo-tetrahydrobiopterin (DH(4), dictyopterin) was detected only in Dictyostelium discoideum, while the isomer L-erythro-tetrahydrobioterin (BH(4)) is common in mammals. To elucidate the mechanism of DH(4) regeneration by D. discoideum dihydropteridine reductase (DicDHPR), we have determined the crystal structure of DicDHPR complexed with NAD(+) at 2.16 Å 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 μM) than mammals. In addition, we have found that rat DHPR as well as DicDHPR could bind to both substrates quinonoid-BH(2) and quinonoid-DH(2) by docking calculations and have confirmed their catalytic activity by in vitro assay.
authors.affiliation: Division of Applied Life Science (BK21 Program), Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Cong
authors.initials: C
authors.lastname: Chen
authors.forename: Hye Lim
authors.initials: HL
authors.lastname: Kim
authors.forename: Ningning
authors.initials: N
authors.lastname: Zhuang
authors.forename: Kyung Hye
authors.initials: KH
authors.lastname: Seo
authors.forename: Ki Hun
authors.initials: KH
authors.lastname: Park
authors.forename: Chang-deok
authors.initials: CD
authors.lastname: Han
authors.forename: Young Shik
authors.initials: YS
authors.lastname: Park
authors.forename: Kon Ho
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D004023:Dictyostelium / Q000201:enzymology*; D004093:Dihydropteridine Reductase / Q000378:metabolism*; D017433:Protein Structure, Secondary; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D001708:Biopterins; C017226:7,8-dihydrobiopterin; D004093:Dihydropteridine Reductase