3orf
From Proteopedia
Crystal Structure of Dihydropteridine Reductase from Dictyostelium discoideum
Structural highlights
FunctionDHPR_DICDI The product of this enzyme, tetrahydrobiopterin (BH-4), is an essential cofactor for phenylalanine, tyrosine, and tryptophan hydroxylases (By similarity). Publication Abstract from PubMedUp 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 2.16A 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+/-0.4muM) 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. STRUCTURED SUMMARY OF PROTEIN INTERACTIONS: DHPRbindstoDHPR by X-ray crystallography(View interaction). Structural insights into the dual substrate specificities of mammalian and Dictyostelium dihydropteridine reductases toward two stereoisomers of quinonoid dihydrobiopterin.,Chen C, Kim HL, Zhuang N, Seo KH, Park KH, Han CD, Park YS, Lee KH FEBS Lett. 2011 Sep 2;585(17):2640-6. Epub 2011 Jul 30. PMID:21819985[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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