Two other class-I GATs, pyridoxal 5'-phosphate (PLP, PDB: 2NV2 ) synthase and carbamoyl phosphate synthetase (CPS, PDB: 1C3O 62 ), have been crystallized in their catalytic forms with the Gln substrate bound. Upon alignment of the Gln substrate reactive carboxamide, the oxyanion strand residue involved in the preformed oxyanion holes in PLP synthase and CPS is more structurally consistent with the IGPS Gly52 than Val51 in Active-ES. Alignment with Inactive Val51-ES shows an even closer alignment, providing evidence that this manually constructed geometry of the IGPS glutaminase active site is feasible. Lastly, glutaminase activation via oxyanion strand repositioning has been proposed for another class-I GAT, aminodeoxychorismate synthase (ADCS), which displays an allosteric response similar to IGPS. Cumulatively, these data are consistent with the computed mechanism and transition structures put forward here. The truncated active-site approach uniquely allowed for the modification of distinct structural features. Such modifications would be inaccessible or much more challenging with alternative modeling approaches (e.g., QM/MM) that explicitly treat the protein environment. This approach is generalizable to other systems in efforts to probe the energetic influence of local structural aspects and highlights the unique applications available to theozyme and cluster modeling.