Structures of aspartate aminotransferases fromTrypanosoma brucei,Leishmania majorandGiardia lamblia

Abstract

The structures of three aspartate aminotransferases (AATs) from eukaryotic pathogens were solved within the Seattle Structural Genomics Center for Infectious Disease (SSGCID). Both the open and closed conformations of AAT were observed. Pyridoxal phosphate was bound to the active siteviaa Schiff base to a conserved lysine. An active-site mutant showed thatTrypanosoma bruceiAAT still binds pyridoxal phosphate even in the absence of the tethering lysine. The structures highlight the challenges for the structure-based design of inhibitors targeting the active site, while showing options for inhibitor design targeting the N-terminal arm.