Structure of Escherichia coli tetrahydrodipicolinate N-succinyltransferase reveals the role of a conserved C-terminal helix in cooperative substrate binding.
Tetrahydrodipicolinate N-succinyltransferase is an enzyme present in many bacteria that catalyzes the first step of the succinylase pathway for the synthesis of meso-diaminopimelate and the amino acid L-lysine. Inhibition of the synthesis of meso-diaminopimelate, a component of peptidoglycan present in the cell wall of bacteria, is a potential route for the development of novel anti-bacterial agents. Here, we report the crystal structure of the DapD tetrahydrodipicolinate N-succinyltransferase from Escherichia coli at 2.0 A resolution. Comparison of the structure with the homologous enzyme from Mycobacterium bovis reveals the C-terminal helix undergoes a large rearrangement upon substrate binding, which contributes to cooperativity in substrate binding.
Nguyen
Long
L
Department of Biochemistry, McGill University, Montréal, 3655 Promenade Sir William Osler, Québec, Canada.
Kozlov
Guennadi
G
Gehring
Kalle
K
D000217:Acyltransferases / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology*; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000217:Acyltransferases; C040777:succinyl-CoA-tetrahydrodipicolinate N-succinyltransferase