Structures of aspartate aminotransferases from Trypanosoma brucei, Leishmania major and Giardia lamblia

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 site via a Schiff base to a conserved lysine. An active-site mutant showed that Trypanosoma brucei AAT 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.

Source: Acta Crystallographica Section F - April 21, 2015 Category: Biochemistry Authors: Abendroth, J.Choi, R.Wall, A.Clifton, M.C.Lukacs, C.M.Staker, B.L.Van Voorhis, W.Myler, P.Lorimer, D.D.Edwards, T.E. Tags: aspartate aminotransferase structural genomics Seattle Structural Genomics Center for Infectious Disease pyridoxalphosphate lysine Giardia lamblia Trypanosoma brucei Leishmania major research communications Source Type: research