Structure and Conformations of GABA-Transaminase Inhibitors. IV. Transition State Analogs

Abstract

Crystal structures of three potential inhibitors [salicylamide derivative C16H15NO4 (5), pyridoxazine C11H16N2O5S (6) and benzoxazone C12H13NO4 (7).H2O] of GABA- transaminase (E.C.2.6.1.19, GABA-T) based on the calculated transition state of GABA-T were determined. The conformational analyses of these structures (non-bonded energies, MNDO,AM1) indicate that they can all fit the transition state in relatively low energy conformations. The crystal structures appear to be close to the calculated minimum energy conformations, except for the salicylamide derivative (5), which features internal hydrogen-bonding. The AM1 parametrization has been used successfully to predict two possible hydrogen-bonded conformations of (5), one of which is found in the crystal structure.