From bacterial to human dihydrouridine synthase: automated structure determination.
Acta Crystallogr D Biol Crystallogr
; 71(Pt 7): 1564-71, 2015 Jul.
Article
en En
| MEDLINE
| ID: mdl-26143927
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 1.9â
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 ß-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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Oxidorreductasas
Límite:
Humans
Idioma:
En
Revista:
Acta Crystallogr D Biol Crystallogr
Año:
2015
Tipo del documento:
Article
País de afiliación:
Reino Unido