The conformational change and active site structure of tetrahydrodipicolinate N-succinyltransferase

Todd W. Beaman, John S. Blanchard, Steven L. Roderick

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Tetrahydrodipicolinate (THDP) N-succinyltransferase catalyzes the conversion of tetrahydrodipicolinate and succinyl-CoA to L-2- (succinylamino)-6-oxopimelate and CoA. This reaction represents the committed step of the succinylase branch of the diaminopimelate/L-lysine biosynthetic pathway by which many bacteria synthesize meso-diaminopimelate, a component of peptidoglycan, and L-lysine from L-aspartate. The crystal structures of THDP succinyltransferase in complex with the substrate/cofactor pairs L-2- aminopimelate/coenzyme A and L-2-amino-6-oxopimelate/coenzyme A have been determined and refined to 2.0 Å resolution. The active site of the enzyme is a long narrow groove located at the interface between two left-handed parallel β-helix (LβH) structural domains of the trimeric enzyme. On binding the amino acid acceptor and cofactor, this groove is covered by residues from the C-terminus of one subunit and a flexible loop excluded from the LβH domain of an adjacent subunit to form a tunnel. This conformational change is directly related to interactions between the enzyme and the bound amino acid substrate and cofactor and serves to shield the ligands from bulk solvent and to orient the nucleophilic amino group of the amino acid acceptor toward the mercaptoethylamine group of the cofactor.

Original languageEnglish (US)
Pages (from-to)10363-10369
Number of pages7
JournalBiochemistry
Volume37
Issue number29
DOIs
StatePublished - Jul 21 1998

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Coenzyme A
Catalytic Domain
Amino Acids
Lysine
Enzymes
Cysteamine
Peptidoglycan
Biosynthetic Pathways
Substrates
Aspartic Acid
Bacteria
Tunnels
Crystal structure
Ligands
succinyl-CoA-tetrahydrodipicolinate N-succinyltransferase

ASJC Scopus subject areas

  • Biochemistry

Cite this

The conformational change and active site structure of tetrahydrodipicolinate N-succinyltransferase. / Beaman, Todd W.; Blanchard, John S.; Roderick, Steven L.

In: Biochemistry, Vol. 37, No. 29, 21.07.1998, p. 10363-10369.

Research output: Contribution to journalArticle

Beaman, Todd W. ; Blanchard, John S. ; Roderick, Steven L. / The conformational change and active site structure of tetrahydrodipicolinate N-succinyltransferase. In: Biochemistry. 1998 ; Vol. 37, No. 29. pp. 10363-10369.
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