FIGURE 2.

OPRT-catalyzed OMP pyrophosphorolysis, ribocation transition state, and transition state mimics. OPRT transition states are characterized by fully dissociated dianionic orotate, an oxacarbenium ion, and weak nucleophile participation. Examples of transition state analogues designed with iminoribitol or pyrrolidine groups as mimics of the oxacarbenium ion and methylene or ethylene linkers to resemble extended C1–N1′ bond distance are shown at the bottom. PRPP, 5′-phospho-d-ribosyl-1-pyrophosphate.