3D Structure of D-Аmino Acid Тransaminase from Aminobacterium colombiense in Complex with D-Cycloserine

Abstract

D-cycloserine inhibits pyridoxal 5'-phosphate (PLP)-dependent enzymes both reversibly and irreversibly. As an alanine racemase inhibitor, D-cycloserine is used in drug therapy in the treatment of tuberculosis. Several products of the interaction of D-cycloserine and PLP in the active site of the enzyme are known. The crystal structure of the complex of PLP-dependent D-amino acid transaminase from the bacteria Aminobacterium colombiense (Amico) with D-cycloserine obtained at a resolution of 1.9 Å is presented, in which the ring-opened adduct of PLP and D-cycloserine was discovered. In addition, the interaction of D-cycloserine with Amico has been characterized by the kinetic and spectral methods, various products of the interaction of D-cycloserine and PLP in the active site of transaminase have been determined, and the coordination of D-cycloserine and PLP adducts in the Amico active site has been analyzed. It is established that the products of the interaction of D-cycloserine with PLP in the Amico active site are several compounds, including PLP and DCS adducts in the cyclic and open forms, oxime formed by PMP and β-aminooxy-D-alanine, and PMP and β-aminooxypyruvate.