Article Metrics


Online attention

From bacterial to human dihydrouridine synthase: automated structure determination

DOI: 10.1107/S1399004715009220 DOI Help
PMID: 26143927 PMID Help

Authors: Fiona Whelan (University of York) , Huw T. Jenkins (Astbury Centre for Structural Molecular Biology, University of Leeds) , Samuel C. Griffiths (University of Oxford) , Robert T. Byrne (Ludwig-Maximilians-University Munich) , Eleanor J. Dodson (The University of York) , Alfred A. Antson (University of York)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acta Crystallographica Section D Biological Crystallography , VOL 71 (7) , PAGES 1564 - 1571

State: Published (Approved)
Published: July 2015
Diamond Proposal Number(s): 1221

Open Access Open Access

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.

Journal Keywords: Dihydrouridine Synthase; X-Ray Crystallography; Mr-Rosetta; Trna Modification; Lung Cancer.

Subject Areas: Biology and Bio-materials

Instruments: I04-Macromolecular Crystallography

Discipline Tags:

Technical Tags: