1W9V

Specificity and affinity of natural product cyclopentapeptide argifin against Aspergillus fumigatus

1W9V の概要

• エントリーDOI: 10.2210/pdb1w9v/pdb
• 関連するPDBエントリー: 1W9P 1W9U
• 関連するBIRD辞書のPRD_ID: PRD_000465
• 分子名称: CHITINASE, ARGIFIN, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: chitinase, argifin, chitinase inhibitors, cyclopentapeptide inhibitors, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: ASPERGILLUS FUMIGATUS; 詳細
• 細胞内の位置: Secreted : Q873X9
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 97287.46

構造登録者

Rao, F.V.,Houston, D.R.,Boot, R.G.,Aerts, J.M.F.G.,Hodkinson, M.,Adams, D.J.,Shiomi, K.,Omura, S.,van Aalten, D.M.F. (登録日: 2004-10-19, 公開日: 2005-01-10, 最終更新日: 2023-12-13)

主引用文献

Rao, F.V.,Houston, D.R.,Boot, R.G.,Aerts, J.M.F.G.,Hodkinson, M.,Adams, D.J.,Shiomi, K.,Omura, S.,Van Aalten, D.M.F.
Specificity and Affinity of Natural Product Cyclopentapeptide Inhibitors Against Aspergillus Fumigatus, Human and Bacterial Chitinases
Chem.Biol., 12:65-, 2005

PubMed Abstract: Family 18 chitinases play key roles in organisms ranging from bacteria to man. There is a need for specific, potent inhibitors to probe the function of these chitinases in different organisms. Such molecules could also provide leads for the development of chemotherapeuticals with fungicidal, insecticidal, or anti-inflammatory potential. Recently, two natural product peptides, argifin and argadin, have been characterized, which structurally mimic chitinase-chitooligosaccharide interactions and inhibit a bacterial chitinase in the nM-mM range. Here, we show that these inhibitors also act on human and Aspergillus fumigatus chitinases. The structures of these enzymes in complex with argifin and argadin, together with mutagenesis, fluorescence, and enzymology, reveal that subtle changes in the binding site dramatically affect affinity and selectivity. The data show that it may be possible to develop specific chitinase inhibitors based on the argifin/argadin scaffolds.

PubMed: 15664516
DOI: 10.1016/J.CHEMBIOL.2004.10.013

実験手法

X-RAY DIFFRACTION (2 Å)