To tackle the cellular drug resistance of thymidylate synthase (TS), the protein-protein interactions involved in TS dimerization and mRNA binding are studied, e.g. by using molecular dynamics simulations.

Figure: Dimeric structure of human thymidylate synthase (PDB code 1hzw: [1]). One monomer is coloured in magenta and the other in cyan. Folate-binding site residues are displayed in green and dUMP-binding site residues in red. NH2 denotes the amino terminus and COOH the carboxy terminus of the protein subunits. A cysteine residue that is critical for mRNA binding (Cys180) is located at the dimer interface [2, 3].




1. Almog R, Waddling CA, Maley F, Maley GF, Van Roey P. Protein Sci. 10: 988-996, 2001
2. Voeller DM, Zajac-Kaye M, Fisher RJ, Allegra CJ. Biophys. Res. Commun. 297: 24-31, 2002
3. Lin X, Liu J, Maley F, Chu E. Nucleic Acid Res. 31: 4882-4887, 2003