Abstract
Cycloserine is a potent inhibitor of pyridoxal phosphate dependent enzymes, similar to gabaculine. The compound was originally expected to inactivate these enzymes by a mechanism-based reaction leading to derivatization of a residue in the active site. In fact, both compounds inactivate these enzymes by reacting covalently with the cofactor, and rearranging to form an irreversible adduct. Analogs of cycloserine and gabaculine have been studied in the expectation that they will react in the same mechanism-based fashion. However, different analogs result in unexpected inactivation products, indicating that the chemistry of the cofactor and the inactivator are not predictable.