2XTK

ChiA1 from Aspergillus fumigatus in complex with acetazolamide

2XTK の概要

• エントリーDOI: 10.2210/pdb2xtk/pdb
• 分子名称: CLASS III CHITINASE CHIA1, 5-ACETAMIDO-1,3,4-THIADIAZOLE-2-SULFONAMIDE, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: hydrolase, gh18
• 由来する生物種: ASPERGILLUS FUMIGATUS
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 70137.84

構造登録者

Schuettelkopf, A.W.,van Aalten, D.M.F. (登録日: 2010-10-11, 公開日: 2011-10-26, 最終更新日: 2024-11-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2 Å)