Aspartate semialdehyde dehydrogenase (ASADH) functions at a critical junction in
the aspartate-biosynthetic pathway and represents a valid target for
antimicrobial drug design. This enzyme catalyzes the NADPH-dependent reductive
dephosphorylation of β-aspartyl phosphate to produce the key intermediate
aspartate semialdehyde. Production of this intermediate represents the first
committed step in the biosynthesis of the essential amino acids methionine,
isoleucine and threonine in fungi, and also the amino acid lysine in bacteria.
The structure of a new fungal form of ASADH from Cryptococcus neoformans has
been determined to 2.6 Å resolution. The overall structure of CnASADH is
similar to those of its bacterial orthologs, but with some critical differences
both in biological assembly and in secondary-structural features that can
potentially be exploited for the development of species-selective drugs.
