New Insight into the Octamer of TYMS Stabilized by Intermolecular Cys43-Disulfide.

ABSTRACT: Thymidylate synthase (TYMS) is an essential enzyme for the de novo synthesis of deoxythymidine monophosphate (dTMP) and has been a primary target for cancer chemotherapy. Although the physical structure of TYMS and the molecular mechanisms of TYMS catalyzing the conversion of deoxyuridine monophosphate (dUMP) to dTMP have been the subject of thorough studies, its oligomeric structure remains unclear. Here, we show that human TYMS not only exists in dimer form but also as an octamer by intermolecular Cys43-disulfide formation. We optimized the expression conditions of recombinant human TYMS using the Escherichia coli system. Using high-performance liquid chromatography⁻tandem mass spectrometry (HPLC⁻MS/MS), we have shown that purified TYMS has catalytic activity for producing dTMP. I

SUBMITTER: Xie D 

PROVIDER: S-EPMC5983622 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature