2XTK

ChiA1 from Aspergillus fumigatus in complex with acetazolamide

Summary for 2XTK

• Entry DOI: 10.2210/pdb2xtk/pdb
• Descriptor: CLASS III CHITINASE CHIA1, 5-ACETAMIDO-1,3,4-THIADIAZOLE-2-SULFONAMIDE, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: hydrolase, gh18
• Biological source: ASPERGILLUS FUMIGATUS
• Total number of polymer chains: 2
• Total formula weight: 70137.84

Authors

Schuettelkopf, A.W.,van Aalten, D.M.F. (deposition date: 2010-10-11, release date: 2011-10-26, Last modification date: 2024-11-13)

Primary citation

Schuttelkopf, A.W.,Gros, L.,Blair, D.E.,Frearson, J.A.,Van Aalten, D.M.F.,Gilbert, I.H.
Acetazolamide-Based Fungal Chitinase Inhibitors.
Bioorg.Med.Chem., 18:8334-, 2010

PubMed Abstract: Chitin is an essential structural component of the fungal cell wall. Chitinases are thought to be important for fungal cell wall remodelling, and inhibition of these enzymes has been proposed as a potential strategy for development of novel anti-fungals. The fungal pathogen Aspergillus fumigatus possesses two distinct multi-gene chitinase families. Here we explore acetazolamide as a chemical scaffold for the inhibition of an A. fumigatus 'plant-type' chitinase. A co-crystal structure of AfChiA1 with acetazolamide was used to guide synthesis and screening of acetazolamide analogues that yielded SAR in agreement with these structural data. Although acetazolamide and its analogues are weak inhibitors of the enzyme, they have a high ligand efficiency and as such are interesting leads for future inhibitor development.

PubMed: 21044846
DOI: 10.1016/J.BMC.2010.09.062

Experimental method

X-RAY DIFFRACTION (2 Å)