The X-ray structure of chitinase from the fungal pathogen Coccidioides immi
tis has been solved to 2.2 Angstrom resolution. Like other members of the c
lass 18 hydrolase family, this 427 residue protein is an eight-stranded bet
a/alpha-barrel. Although lacking an N-terminal chitin anchoring domain, the
enzyme closely resembles the chitinase from Serratia marcescens. Among the
conserved features are three cis peptide bonds, all involving conserved ac
tive site residues. The active site is formed from conserved residues such
as tryptophans 47, 131, 315, 378, tyrosines 239 and 293, and arginines 52 a
nd 295. Glu171 is the catalytic acid in the hydrolytic mechanism; it was mu
tated to a Gin, and activity was abolished. Allosamidin is a substrate anal
og that strongly inhibits the class 18 enzymes. Its binding to the chitinas
e hevamine has been observed, and we used conserved structural features of
the two enzymes to predict the inhibitors binding to the fungal enzyme.