3ORF

Crystal Structure of Dihydropteridine Reductase from Dictyostelium discoideum

Summary for 3ORF

• Entry DOI: 10.2210/pdb3orf/pdb
• Related: 1DHR 1DIR 1HDR 1OOE
• Descriptor: Dihydropteridine reductase, NICOTINAMIDE-ADENINE-DINUCLEOTIDE (3 entities in total)
• Functional Keywords: alpha-beta-alpha sandwich, rossmann fold, oxidoreductase (acting on nadh), nadh binding, oxidoreductase
• Biological source: Dictyostelium discoideum (Slime mold)
• Total number of polymer chains: 4
• Total formula weight: 110050.18

Authors

Chen, C.,Zhuang, N.N.,Seo, K.H.,Park, Y.S.,Lee, K.H. (deposition date: 2010-09-07, release date: 2011-07-27, Last modification date: 2023-11-01)

Primary citation

Chen, C.,Kim, H.L.,Zhuang, N.,Seo, K.H.,Park, K.H.,Han, C.-D.,Park, Y.S.,Lee, K.H.
Structural insights into the dual substrate specificities of mammalian and Dictyostelium dihydropteridine reductases toward two stereoisomers of quinonoid dihydrobiopterin
Febs Lett., 585:2640-2646, 2011

PubMed 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.

PubMed: 21819985
DOI: 10.1016/j.febslet.2011.07.018

Experimental method

X-RAY DIFFRACTION (2.16 Å)