The X-ray structure of a chitinase from the pathogenic fungus Coccidioidesimmitis

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.