7STM

Chitin Synthase 2 from Candida albicans bound to UDP-GlcNAc

7STM の概要

• エントリーDOI: 10.2210/pdb7stm/pdb
• EMDBエントリー: 25433
• 分子名称: Chitin synthase, 1,2-Distearoyl-sn-glycerophosphoethanolamine, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: chitin synthesis, glycosyltransferase, membrane protein, transferase
• 由来する生物種: Candida albicans
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 245844.29

構造登録者

Ren, Z.,Chhetri, A.,Lee, S.,Yokoyama, K. (登録日: 2021-11-14, 公開日: 2022-07-13, 最終更新日: 2025-06-04)

主引用文献

Ren, Z.,Chhetri, A.,Guan, Z.,Suo, Y.,Yokoyama, K.,Lee, S.Y.
Structural basis for inhibition and regulation of a chitin synthase from Candida albicans.
Nat.Struct.Mol.Biol., 29:653-664, 2022

PubMed Abstract: Chitin is an essential component of the fungal cell wall. Chitin synthases (Chss) catalyze chitin formation and translocation across the membrane and are targets of antifungal agents, including nikkomycin Z and polyoxin D. Lack of structural insights into the action of these inhibitors on Chs has hampered their further development to the clinic. We present the cryo-EM structures of Chs2 from Candida albicans (CaChs2) in the apo, substrate-bound, nikkomycin Z-bound, and polyoxin D-bound states. CaChs2 adopts a unique domain-swapped dimer configuration where a conserved motif in the domain-swapped region controls enzyme activity. CaChs2 has a dual regulation mechanism where the chitin translocation tunnel is closed by the extracellular gate and plugged by a lipid molecule in the apo state to prevent non-specific leak. Analyses of substrate and inhibitor binding provide insights into the chemical logic of Chs inhibition, which can guide Chs-targeted antifungal development.

PubMed: 35788183
DOI: 10.1038/s41594-022-00791-x

実験手法

ELECTRON MICROSCOPY (3.02 Å)