Background: N-acetylneuraminate lyase catalyzes the cleavage of N-acet
ylneuraminic acid (sialic acid) to form pyruvate and N-acetyl-D-mannos
amine. The enzyme plays an important role in the regulation of sialic
acid metabolism in bacteria. The reverse reaction can be exploited for
die synthesis of sialic acid and some of its derivatives. Results: Th
e structure of the enzyme from Escherichia coli has been determined to
2.2angstrom resolution by X-ray crystallography. The enzyme is shown
to be a tetramer, in which each subunit consists of an alpha/beta-barr
el domain followed by a carboxy-terminal extension of three alpha-heli
ces. Conclusions: The active site of the enzyme is tentatively identif
ied as a pocket at the carboxy-terminal end of the eight-stranded beta
-barrel. Lys165 lies within this pocket and is probably the reactive r
esidue which forms a Schiff base intermediate with the substrate. The
sequence of N-acetylneuraminate lyase has similarities to those of dih
ydrodipicolinate synthase and MosA (an enzyme implicated in rhizopine
synthesis) suggesting that these last two enzymes share a similar stru
cture to N-acetylneuraminate lyase.