Send to

Choose Destination
Biochemistry. 1997 Jan 7;36(1):24-33.

Reaction mechanism of Escherichia coli dihydrodipicolinate synthase investigated by X-ray crystallography and NMR spectroscopy.

Author information

Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Martinsried, FRG.


Dihydrodipicolinate synthase (DHDPS) catalyzes the condensation of pyruvate with L-aspartate beta-semialdehyde. It is the first enzyme unique to the diaminopimelate pathway of lysine biosynthesis. Here we present the crystal structures of five complexes of Escherichia coli DHDPS with substrates, substrate analogs, and inhibitors. These include the complexes of DHDPS with (1) pyruvate, (2) pyruvate and the L-aspartate beta-semialdehyde analog succinate beta-semialdehyde, (3) the inhibitor alpha-ketopimelic acid, (4) dipicolinic acid, and (5) the natural feedback inhibitor L-lysine. The kinetics of inhibition were determined, and the binding site of the L-lysine was identified. NMR experiments were conducted in order to elucidate the nature of the product of the reaction catalyzed by DHDPS. By this method, (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinic acid is identified as the only product. A reaction mechanism for DHDPS is proposed, and important features for inhibition are identified.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for American Chemical Society
Loading ...
Support Center