Quantum mechanical methods are used to investigate the chemical steps during the bifunctional (glycosylase and beta-lyase) activity of bacterial FPG DNA glycosylase, which removes the major oxidation product (8-oxoguanine) from DNA as part of the base excision repair process. To facilitate investigation of all potential pathways, the smallest chemically relevant model is implemented, namely a modified OG nucleoside-3'-monophosphate and a truncated proline nucleophile. Potential energy surfaces are characterized with SMD-M06-2X/6-311+G(2df,2p)//PCM-B3LYP/6-31G(d) and compared to a previous study on the analogues human enzyme (hOgg1), which uses a lysine nucleophile (Kellie, J. L.; Wetmore, S. D. J. Phys. Chem. B 2012, 116, 10786-10797). Our large calculated barriers indicate that FPG must actively catalyze the three main phases of the overall reaction, namely, deglycosylation, (deoxyribose) ring-opening, and b-elimination, and provide clues about how this is achieved through comparison to accurate crystal structures. The main conclusions about key mechanistic steps hold true regardless of the nucleophile, suggesting that most major differences in the relative activity of FPG and hOgg1 are primarily due to other active site residues. Nevertheless, support for possible monofunctional (deglycosylation only) activity is only evident when lysine is the nucleophile. This finding agrees with experimental observations of monofunctional activity of hOgg1 and further supports the broadly accepted bifunctional activity of FPG.