EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structural basis for inhibition and regulation of a chitin synthase from Candida albicans.
ジャーナル・号・ページ	Nat Struct Mol Biol, Vol. 29, Issue 7, Page 653-664, Year 2022
掲載日	2022年7月4日
著者	Zhenning Ren / Abhishek Chhetri / Ziqiang Guan / Yang Suo / Kenichi Yokoyama / Seok-Yong Lee /
PubMed 要旨	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 ...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.
リンク	Nat Struct Mol Biol / PubMed:35788183 / PubMed Central
手法	EM (単粒子)
解像度	2.95 - 3.19 Å
構造データ	25432 7stl EMDB-25432, PDB-7stl: Chitin Synthase 2 from Candida albicans at the apo state 手法: EM (単粒子) / 解像度: 2.95 Å 25433 7stm EMDB-25433, PDB-7stm: Chitin Synthase 2 from Candida albicans bound to UDP-GlcNAc 手法: EM (単粒子) / 解像度: 3.02 Å 25434 7stn EMDB-25434, PDB-7stn: Chitin Synthase 2 from Candida albicans bound to Nikkomycin Z 手法: EM (単粒子) / 解像度: 3.19 Å 25435 7sto EMDB-25435, PDB-7sto: Chitin Synthase 2 from Candida albicans bound to polyoxin D 手法: EM (単粒子) / 解像度: 3.15 Å
化合物	ChemComp-3PE: 1,2-Distearoyl-sn-glycerophosphoethanolamine / DSPE / リン脂質YM ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-UD1: URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE / UDP-GlcNAc ChemComp-BGI: (2S)-{[(2S,3S,4S)-2-amino-4-hydroxy-4-(5-hydroxypyridin-2-yl)-3-methylbutanoyl]amino}[(2R,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxyoxolan-2-yl]acetic acid (non-preferred name) / ニッコマイシンZ / 薬剤, 抗真菌剤YM ChemComp-BJ9: 1-{(2R,3R,4S,5R)-5-[(S)-{[(2S,3S,4S)-2-amino-5-(carbamoyloxy)-3,4-dihydroxypentanoyl]amino}(carboxy)methyl]-3,4-dihydroxyoxolan-2-yl}-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (non-preferred name) / ポリオキシンD / 抗生剤*YM
由来	candida albicans (酵母)
キーワード	MEMBRANE PROTEIN / chitin synthesis / glycosyltransferase / TRANSFERASE / Nikkomycin Z / polyoxin D