4XP7

Crystal structure of Human tRNA dihydrouridine synthase 2

Summary for 4XP7

• Entry DOI: 10.2210/pdb4xp7/pdb
• Descriptor: tRNA-dihydrouridine(20) synthase [NAD(P)+]-like, 1-DEOXY-1-(7,8-DIMETHYL-2,4-DIOXO-3,4-DIHYDRO-2H-BENZO[G]PTERIDIN-1-ID-10(5H)-YL)-5-O-PHOSPHONATO-D-RIBITOL (3 entities in total)
• Functional Keywords: trna, dus, oxidoreductase
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : Q9NX74
• Total number of polymer chains: 1
• Total formula weight: 39128.89

Authors

Whelan, F.,Jenkins, H.T.,Griffiths, S.,Byrne, R.T.,Dodson, E.J.,Antson, A.A. (deposition date: 2015-01-16, release date: 2015-01-28, Last modification date: 2024-10-23)

Primary citation

Whelan, F.,Jenkins, H.T.,Griffiths, S.C.,Byrne, R.T.,Dodson, E.J.,Antson, A.A.
From bacterial to human dihydrouridine synthase: automated structure determination.
Acta Crystallogr.,Sect.D, 71:1564-1571, 2015

PubMed Abstract: The reduction of uridine to dihydrouridine at specific positions in tRNA is catalysed by dihydrouridine synthase (Dus) enzymes. Increased expression of human dihydrouridine synthase 2 (hDus2) has been linked to pulmonary carcinogenesis, while its knockdown decreased cancer cell line viability, suggesting that it may serve as a valuable target for therapeutic intervention. Here, the X-ray crystal structure of a construct of hDus2 encompassing the catalytic and tRNA-recognition domains (residues 1-340) determined at 1.9 Å resolution is presented. It is shown that the structure can be determined automatically by phenix.mr_rosetta starting from a bacterial Dus enzyme with only 18% sequence identity and a significantly divergent structure. The overall fold of the human Dus2 is similar to that of bacterial enzymes, but has a larger recognition domain and a unique three-stranded antiparallel β-sheet insertion into the catalytic domain that packs next to the recognition domain, contributing to domain-domain interactions. The structure may inform the development of novel therapeutic approaches in the fight against lung cancer.

PubMed: 26143927
DOI: 10.1107/S1399004715009220

Experimental method

X-RAY DIFFRACTION (1.9 Å)