Skip to main content
. Author manuscript; available in PMC: 2019 Jul 9.
Published in final edited form as: Chem Rev. 2018 Oct 18;118(22):11194–11258. doi: 10.1021/acs.chemrev.8b00369

Figure 33.

Figure 33

Reaction, transition state, and proposed transition state analogue inhibitors for P. falciparum and human OPRT-catalyzed OMP pyrophosphorolysis. OPRT transition states are characterized by fully dissociated dianionic orotate, a ribocation, and weak nucleophile (PPi) participation. Iminoribitol, pyrrolidine, or acyclic ribocation groups as mimics of the ribocation were proposed. Methylene or ethylene linkers resemble the extended bond distance to approximate the transition state. PRPP, 5-phospho-α-D-ribosyl 1-pyrophosphate. Reproduced with permission from ref 222. Copyright 2013 American Society for Biochemistry and Molecular Biology.