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1.  Screening-based discovery of Aspergillus fumigatus plant-type chitinase inhibitors 
Febs Letters  2014;588(17):3282-3290.
Highlights
•We performed a high-throughput screen of 60,000 compounds against A. fumigatus chitinase A1.•Novel low micromolar competitive inhibitors were identified.•These represent the most potent selective plant-type A. fumigatus chitinase inhibitors to date.•We provide new tools for probing chitinase inhibition in A. fumigatus and other fungi.
A limited therapeutic arsenal against increasing clinical disease due to Aspergillus spp. necessitates urgent characterisation of new antifungal targets. Here we describe the discovery of novel, low micromolar chemical inhibitors of Aspergillus fumigatus family 18 plant-type chitinase A1 (AfChiA1) by high-throughput screening (HTS). Analysis of the binding mode by X-ray crystallography confirmed competitive inhibition and kinetic studies revealed two compounds with selectivity towards fungal plant-type chitinases. These inhibitors provide new chemical tools to probe the effects of chitinase inhibition on A. fumigatus growth and virulence, presenting attractive starting points for the development of further potent drug-like molecules.
doi:10.1016/j.febslet.2014.07.015
PMCID: PMC4158421  PMID: 25063338
HTS, high-throughput screen/screening; GlcNAc, N-acetylglucosamine; AfChiA1, Aspergillus fumigatus chitinase A1; ScCTS1, Saccharomyces cerevisiae chitinase 1; AfChiB, Aspergillus fumigatus chitinase B1; AMCase, acidic mammalian chitinase; HsCHT, Homo sapiens chitotriosidase (chitinase 1); PI, percentage inhibition; Chitinases; Inhibitors; High-throughput screen (HTS); Aspergillus fumigatus
2.  Purification, crystallization and preliminary X-ray diffraction data of UDP-galactopyranose mutase from Aspergillus fumigatus  
The cloning, overexpression, purification, crystallization and preliminary X-ray diffraction data are described for UDP-galactopyranose mutase, an enzyme involved in cell-wall synthesis in A. fumigatus.
Aspergillus fumigatus UDP-galactopyranose mutase (AfUGM) is a potential drug target involved in the synthesis of the cell wall of this fungal pathogen. AfUGM was recombinantly produced in Escherichia coli, purified and crystallized by the sitting-drop method, producing orthorhombic crystals that diffracted to a resolution of 3.25 Å. The crystals contained four molecules per asymmetric unit and belonged to space group P212121, with unit-cell parameters a = 127.72, b = 134.30, c = 173.84 Å. Incorporation of selenomethionine was achieved, but the resulting crystals did not allow solution of the phase problem.
doi:10.1107/S1744309112017915
PMCID: PMC3370916  PMID: 22684076
UDP-galactopyranose mutase; Aspergillus fumigatus

Results 1-2 (2)