The conformational change and active site structure of tetrahydrodipicolinate N-succinyltransferase.
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 A resolution. The active site of the enzyme is a long narrow groove located at the interface between two left-handed parallel beta-helix (LbetaH) 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 LbetaH 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.
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
T W
TW
Beaman
J S
JS
Blanchard
S L
SL
Roderick
D000217:Acyltransferases / Q000737:chemistry* / Q000378:metabolism*; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D003065:Coenzyme A / Q000737:chemistry / Q000378:metabolism; D003460:Crystallization; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity
D000596:Amino Acids; D000217:Acyltransferases; C040777:succinyl-CoA-tetrahydrodipicolinate N-succinyltransferase; D003065:Coenzyme A