QM/MM calculations suggest a novel intermediate following the proton abstraction catalyzed by thymidylate synthase.

ABSTRACT: The cleavage of covalent C-H bonds is one of the most energetically demanding, yet biologically essential, chemical transformations. Two C-H bond cleavages are involved in the reaction catalyzed by thymidylate synthase (TSase), which provides the sole de novo source of thymidylate (i.e., the DNA base T) for most organisms. Our QM/MM free energy calculations show that the C-H → O proton transfer has three transition states that are energetically similar but structurally diverse. These characteristics are different from our previous calculation results on the C-H → C hydride transfer, providing an explanation for differences in temperature dependences of KIEs on these two C-H bond activation steps. The calculations also suggest that the traditionally proposed covalent bond between the protei

SUBMITTER: Wang Z 

PROVIDER: S-EPMC3634118 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature