1KGQ

Crystal Structure of Tetrahydrodipicolinate N-Succinyltransferase in Complex with L-2-aminopimelate and Succinamide-CoA

Summary for 1KGQ

• Entry DOI: 10.2210/pdb1kgq/pdb
• Related: 1KGT 1TDT 2TDT 3TDT
• Descriptor: 2,3,4,5-TETRAHYDROPYRIDINE-2-CARBOXYLATE N-SUCCINYLTRANSFERASE, (2S)-2-aminoheptanedioic acid, SUCCINAMIDE-COA, ... (4 entities in total)
• Functional Keywords: left-handed parallel beta helix, transferase
• Biological source: Mycobacterium bovis
• Cellular location: Cytoplasm: P56220
• Total number of polymer chains: 1
• Total formula weight: 30944.73

Authors

Beaman, T.W.,Vogel, K.W.,Drueckhammer, D.G.,Blanchard, J.S.,Roderick, S.L. (deposition date: 2001-11-28, release date: 2002-04-03, Last modification date: 2024-02-14)

Primary citation

Beaman, T.W.,Vogel, K.W.,Drueckhammer, D.G.,Blanchard, J.S.,Roderick, S.L.
Acyl group specificity at the active site of tetrahydridipicolinate N-succinyltransferase.
Protein Sci., 11:974-979, 2002

PubMed Abstract: Tetrahydrodipicolinate N-succinyltransferase (DapD) catalyzes the succinyl-CoA-dependent acylation of L-2-amino-6-oxopimelate to 2-N-succinyl-6-oxopimelate as part of the succinylase branch of the meso-diaminopimelate/lysine biosynthetic pathway of bacteria, blue-green algae, and plants. This pathway provides meso-diaminopimelate as a building block for cell wall peptidoglycan in most bacteria, and is regarded as a target pathway for antibacterial agents. We have solved the X-ray crystal structures of DapD in ternary complexes with pimelate/succinyl-CoA and L-2-aminopimelate with the nonreactive cofactor analog, succinamide-CoA. These structures define the binding conformation of the cofactor succinyl group and its interactions with the enzyme and place its thioester carbonyl carbon in close proximity to the nucleophilic 2-amino group of the acceptor, in support of a direct attack ternary complex mechanism. The acyl group specificity differences between homologous tetrahydrodipicolinate N-acetyl- and N-succinyltransferases can be rationalized with reference to at least three amino acids that interact with or give accessible active site volume to the cofactor succinyl group. These residues account at least in part for the substrate specificity that commits metabolic intermediates to either the succinylase or acetylase branches of the meso-diaminopimelate/lysine biosynthetic pathway.

PubMed: 11910040
DOI: 10.1110/ps.4310102

Experimental method

X-RAY DIFFRACTION (2 Å)