Crystal structures of thymidylate synthase from nematodes, Trichinella spiralis and Caenorhabditis elegans, as a potential template for species-specific drug design

• Main Authors: Dowierciał Anna, Wilk Piotr, Rypniewski Wojciech, Frączyk Tomasz, Jarmuła Adam, Banaszak Katarzyna, Dąbrowska Magdalena, Cieśla Joanna, Rode Wojciech
• Format: Article
• Language: English
• Published: De Gruyter 2013-06-01
• Series: Pteridines
• Subjects: 3d structure; nematode; thymidylate synthase; enzymes: thymidylate synthase (ec 2.1.1.45); pdb reference: trichinella spiralis thymidylate synthase-dump complex, 4g9u; caenorhabditis elegans thymidylate synthase-dump complex, 4irr
• Online Access: https://doi.org/10.1515/pterid-2013-0011
• ISSN: 0933-4807; 2195-4720

Crystal structures were solved of the binary complexes Trichinella spiralis and Caenorhabditis elegans thymidylate synthases with deoxyuridine monophosphate (dUMP), with crystals obtained by the vapor diffusion method in hanging drops. For the T. spiralis thymidylate synthase-dUMP complex, the diffraction data were collected at the BESSY Synchrotron to 1.9 Å resolution. The crystal belongs to the space group P1 with two dimers in the asymmetric unit (ASU). For the C. elegans TS-dUMP complex crystal, the diffraction data were collected at the BESSY Synchrotron to 2.48 Å resolution, and the crystal belongs to the space group P 32 2 1, with two monomers (one dimer) in the ASU. Structural comparisons were made of both structures and each of them with the corresponding mouse thymidylate synthase complex.