Crystallization and preliminary X-ray analysis of mycophenolic acid-resistant and mycophenolic acid-sensitive forms of IMP dehydrogenase from the human fungal pathogen Cryptococcus.
Fungal human pathogens such as Cryptococcus neoformans are becoming an increasingly prevalent cause of human morbidity and mortality owing to the increasing numbers of susceptible individuals. The few antimycotics available to combat these pathogens usually target fungal-specific cell-wall or membrane-related components; however, the number of these targets is limited. In the search for new targets and lead compounds, C. neoformans has been found to be susceptible to mycophenolic acid through its target inosine monophosphate dehydrogenase (IMPDH); in contrast, a rare subtype of the related C. gattii is naturally resistant. Here, the expression, purification, crystallization and preliminary crystallographic analysis of IMPDH complexed with IMP and NAD+ is reported for both of these Cryptococcus species. The crystals of IMPDH from both sources had the symmetry of the tetragonal space group I422 and diffracted to a resolution of 2.5 A for C. neoformans and 2.6 A for C. gattii.
Morrow
Carl A
CA
Centre for Infectious Disease Research, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia.
Stamp
Anna
A
Valkov
Eugene
E
Kobe
Bostjan
B
Fraser
James A
JA
D003455:Cryptococcus neoformans / Q000187:drug effects / Q000201:enzymology*; D003460:Crystallization; D018360:Crystallography, X-Ray; D025141:Drug Resistance, Fungal / Q000187:drug effects; D007168:IMP Dehydrogenase / Q000737:chemistry*; D007291:Inosine Monophosphate / Q000737:chemistry; D009173:Mycophenolic Acid / Q000494:pharmacology*
D007291:Inosine Monophosphate; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid
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