InterPro domain: IPR035587

This entry represents a dihydrouridine synthase-like (DUS-like) FMN-binding domain [ 1 ]. Proteins containing this domain catalyse the reduction of the 5,6-double bond of a uridine residue on tRNA. Dihydrouridine modification of tRNA is widely observed in prokaryotes and eukaryotes, and also in some archaea. Most dihydrouridines are found in the D loop of t-RNAs. The role of dihydrouridine in tRNA is currently unknown, but may increase conformational flexibility of the tRNA. It is likely that different family members have different substrate specificities, which may overlap [ 2 , 3 ]. 1VHN, a putative flavin oxidoreductase, has high sequence similarity to DUS. The enzymatic mechanism of 1VHN is not known at the present [ 4 ].

Dihydrouridine synthases (Dus) is a large family of flavoenzymes comprising eight subfamilies. They catalyse the NADPH-dependent synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs. Mainly, they contain two functional conserved domains, an N-terminal catalytic domain (TBD) adopting a TIM barrel fold and a unique C-terminal helical domain (HD) devoted to tRNA recognition. However, DUS2 is distinguished from its paralogues and its fungi orthologues by the acquisition of an additional domain, a double stranded RNA binding domain (dsRBD), which serves as the main tRNA binding module [ 4 , 5 ].

1. The 1.59 A resolution crystal structure of TM0096, a flavin mononucleotide binding protein from Thermotoga maritima. Proteins 55, 772-4
2. A conserved family of Saccharomyces cerevisiae synthases effects dihydrouridine modification of tRNA. RNA 8, 370-81
3. Identification of the tRNA-dihydrouridine synthase family. J. Biol. Chem. 277, 25090-5
4. Electrostatic Potential in the tRNA Binding Evolution of Dihydrouridine Synthases. Biochemistry 57, 5407-5414
5. Molecular basis for transfer RNA recognition by the double-stranded RNA-binding domain of human dihydrouridine synthase 2. Nucleic Acids Res 47, 3117-3126