The meso-diaminopimelate decarboxylase (DAPDC, EC catalyzes the final step of L-lysine biosynthesis in bacteria
and is regarded as a target for the discovery of antibiotics.
Here we report the 2.3A˚ crystal structure of DAPDC from Helicobacter
pylori (HpDAPDC). The structure, in which the product
L-lysine forms a Schiff base with the cofactor pyridoxal
5-phosphate, provides structural insight into the substrate
specificity and catalytic mechanism of the enzyme, and implies
that the carboxyl to be cleaved locates at the si face of the cofactor.
To our knowledge, this might be the first reported external
aldimine of DAPDC. Moreover, the active site loop of
HpDAPDC is in a “down” conformation and shields the ligand
from solvent. Mutations of Ile148 from the loop greatly impaired
the catalytic efficiency. Combining the structural analysis of the
I148L mutant, we hypothesize that HpDAPDC adopts an
induced-fit catalytic mechanism in which this loop cycles
through “down” and “up” conformations to stabilize intermediates
and release product, respectively. Our work is expected to
provide clues for designing specific inhibitors of DAPDC.