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	Substrate recognition diversity and transport dynamics of ABCC1.
ジャーナル・号・ページ	Nat Commun, Vol. 16, Issue 1, Page 10499, Year 2025
掲載日	2025年11月25日
著者	Panpan Sun / Kexin Liu / Linnan Zhang / Qixiang Zhang / Yina Gao / Zhaolong Li / Yalan Zhu / Songqing Liu / Liguo Zhang / Ang Gao / Pu Gao /
PubMed 要旨	ABCC1 is an ATP-binding cassette (ABC) transporter that exports diverse endogenous and exogenous substrates, conferring resistance to many anticancer drugs and mediating various physiological ...ABCC1 is an ATP-binding cassette (ABC) transporter that exports diverse endogenous and exogenous substrates, conferring resistance to many anticancer drugs and mediating various physiological functions. Here, we present ten cryo-EM structures of ABCC1 in different functional states, providing systematic insights into its substrate recognition diversity and transport dynamics. ABCC1 utilizes a plastic bipartite substrate-binding pocket and a substrate-induced conformational flexibility to accommodate molecules with diverse properties, including bimolecular glutathione (GSH)-substrate pairs, GSH conjugates, and GSH-independent cyclic dinucleotides. A herein characterized substrate-releasing intermediate state reveals ATP-mediated overall conformational transitions and detailed pocket reorganization during substrate loading, pre-release, and post-release. Unexpectedly, we identify a sequential nucleotide release mechanism where the hydrolysis product ADP, rather than unhydrolyzed ATP, releases first, priming the transporter for turnover and resetting. Complemented by mutagenesis and functional assays, these findings provide a complete framework for understanding ABCC1's molecular basis and offer a foundation for developing next-generation modulators.
リンク	Nat Commun / PubMed:41290683 / PubMed Central
手法	EM (単粒子)
解像度	2.95 - 3.7 Å
構造データ	63055 9lg6 EMDB-63055, PDB-9lg6: bovine ABCC1 bound to CDAS 手法: EM (単粒子) / 解像度: 3.7 Å 63056 9lg7 EMDB-63056, PDB-9lg7: bovine ABCC1 bound to 2'3'-CDAS (in the presence of GSH) 手法: EM (単粒子) / 解像度: 3.64 Å 63057 9lg8 EMDB-63057, PDB-9lg8: bovine ABCC1 bound to estrogen sulfate and GSH 手法: EM (単粒子) / 解像度: 3.55 Å 63058 9lg9 EMDB-63058, PDB-9lg9: bovine ABCC1 bound to GSSG 手法: EM (単粒子) / 解像度: 3.56 Å 63059 9lga EMDB-63059, PDB-9lga: bovine ABCC1 bound to verapamil and GSH 手法: EM (単粒子) / 解像度: 3.36 Å 63060 9lgb EMDB-63060, PDB-9lgb: bovine ABCC1 bound to leukotriene C4 手法: EM (単粒子) / 解像度: 3.34 Å 63061 9lgc EMDB-63061, PDB-9lgc: bovine ABCC1 bound to vincristine and GSH 手法: EM (単粒子) / 解像度: 2.95 Å 63062 9lgd EMDB-63062, PDB-9lgd: wild-type bovine ABCC1 under an active turnover conformation with unhydrolyzed ATP bound and hydrolyzed ADP released 手法: EM (単粒子) / 解像度: 3.29 Å 63063 9lge EMDB-63063, PDB-9lge: wild-type bovine ABCC1 bound to two ATP molecules -1 手法: EM (単粒子) / 解像度: 3.21 Å 63064 9lgf EMDB-63064, PDB-9lgf: wild type bovine ABCC1 bound to two ATP molecules -2 手法: EM (単粒子) / 解像度: 3.01 Å
化合物	ChemComp-GJF: (1~{R},3~{S},6~{R},8~{R},9~{R},10~{S},12~{S},15~{R},17~{R},18~{R})-8,17-bis(6-aminopurin-9-yl)-3,12-bis(oxidanylidene)-3,12-bis(sulfanyl)-2,4,7,11,13,16-hexaoxa-3$l^{5},12$l^{5}-diphosphatricyclo[13.2.1.0^{6,10}]octadecane-9,18-diol ChemComp-FY5: estrone 3-sulfate / 薬剤, ホルモンYM ChemComp-GSH: GLUTATHIONE ChemComp-GDS: OXIDIZED GLUTATHIONE DISULFIDE ChemComp-4YH: (2S)-2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile ChemComp-LTX: (5~{S},6~{R},7~{E},9~{E},11~{Z},14~{Z})-6-[(2~{R})-2-[[(4~{S})-4-azanyl-5-oxidanyl-5-oxidanylidene-pentanoyl]amino]-3-( ChemComp-R1Q: vincristine ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP, エネルギー貯蔵分子YM ChemComp-MG: Unknown entry
由来	bos taurus (ウシ)
キーワード	PROTEIN TRANSPORT / ABC transporter / inward-open ABCC1 / CDAS / 2'3'-CDAS / estrogen sulfate / GSH / GSSG / verapamil / LTC4 / vincristine / active ABCC1 / ATP / outward-open ABCC1