title: Structures of aspartate aminotransferases from Trypanosoma brucei, Leishmania major and Giardia 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 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.
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease, http://www.ssgcid.org, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Abendroth
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease, http://www.ssgcid.org, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Choi
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease, http://www.ssgcid.org, USA.
authors.forename: Abigail
authors.initials: A
authors.lastname: Wall
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease, http://www.ssgcid.org, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Clifton
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease, http://www.ssgcid.org, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Lukacs
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease, http://www.ssgcid.org, USA.
authors.forename: Bart L
authors.initials: BL
authors.lastname: Staker
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease, http://www.ssgcid.org, USA.
authors.forename: Wesley
authors.initials: W
authors.lastname: Van Voorhis
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease, http://www.ssgcid.org, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Myler
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease, http://www.ssgcid.org, USA.
authors.forename: Don D
authors.initials: DD
authors.lastname: Lorimer
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease, http://www.ssgcid.org, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Edwards
mesh_terms: D001219:Aspartate Aminotransferases / Q000737:chemistry*; D003460:Crystallization; D016829:Giardia lamblia / Q000737:chemistry* / Q000201:enzymology; D018320:Leishmania major / Q000737:chemistry* / Q000201:enzymology; D017433:Protein Structure, Secondary; D014346:Trypanosoma brucei brucei / Q000737:chemistry* / Q000201:enzymology
chemical_list: D001219:Aspartate Aminotransferases
keywords: Giardia lamblia; Leishmania major; Seattle Structural Genomics Center for Infectious Disease; Trypanosoma brucei; aspartate aminotransferase; pyridoxalphosphate lysine; structural genomics; transferase