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	Cryo-EM Analysis of the Conformational Landscape of Human P-glycoprotein (ABCB1) During its Catalytic Cycle.
ジャーナル・号・ページ	Mol Pharmacol, Vol. 90, Issue 1, Page 35-41, Year 2016
掲載日	2016年5月11日
著者	Gabriel A Frank / Suneet Shukla / Prashant Rao / Mario J Borgnia / Alberto Bartesaghi / Alan Merk / Aerfa Mobin / Lothar Esser / Lesley A Earl / Michael M Gottesman / Di Xia / Suresh V Ambudkar / Sriram Subramaniam /
PubMed 要旨	The multidrug transporter P-glycoprotein (P-gp, ABCB1) is an ATP-dependent pump that mediates the efflux of structurally diverse drugs and xenobiotics across cell membranes, affecting drug ...The multidrug transporter P-glycoprotein (P-gp, ABCB1) is an ATP-dependent pump that mediates the efflux of structurally diverse drugs and xenobiotics across cell membranes, affecting drug pharmacokinetics and contributing to the development of multidrug resistance. Structural information about the conformational changes in human P-gp during the ATP hydrolysis cycle has not been directly demonstrated, although mechanistic information has been inferred from biochemical and biophysical studies conducted with P-gp and its orthologs, or from structures of other ATP-binding cassette transporters. Using single-particle cryo-electron microscopy, we report the surprising discovery that, in the absence of the transport substrate and nucleotides, human P-gp can exist in both open [nucleotide binding domains (NBDs) apart; inward-facing] and closed (NBDs close; outward-facing) conformations. We also probe conformational states of human P-gp during the catalytic cycle, and demonstrate that, following ATP hydrolysis, P-gp transitions through a complete closed conformation to a complete open conformation in the presence of ADP.
リンク	Mol Pharmacol / PubMed:27190212 / PubMed Central
手法	EM (単粒子)
解像度	12.0 - 22.0 Å
構造データ	EMDB-3421: Electron cryo-microscopy of human P-glycoprotein: Apo state - closed conformation 手法: EM (単粒子) / 解像度: 12.0 Å EMDB-3422: human P-Glycoprote in open conformation 手法: EM (単粒子) / 解像度: 17.0 Å EMDB-3423: Electron cryo-microscopy of human P-glycoprotein: Apo state - closed conformation 手法: EM (単粒子) / 解像度: 22.0 Å EMDB-3424: Electron cryo-microscopy of human P-glycoprotein: Apo state - open conformation 手法: EM (単粒子) / 解像度: 22.0 Å EMDB-3425: Electron cryo-microscopy of human P-glycoprotein: ATP bound - closed conformation 手法: EM (単粒子) / 解像度: 19.0 Å EMDB-3426: Electron cryo-microscopy of human P-glycoprotein: ATP bound state - open conformation 手法: EM (単粒子) / 解像度: 21.0 Å EMDB-3427: Electron cryo-microscopy of human P-glycoprotein: Bound to ADP-Vi - closed conformation 手法: EM (単粒子) / 解像度: 20.0 Å EMDB-3428: Electron cryo-microscopy of human P-glycoprotein: ADP bound state - open conformation #1 手法: EM (単粒子) / 解像度: 21.0 Å EMDB-3429: Electron cryo-microscopy of human P-glycoprotein: ADP bound state - open conformation #2 手法: EM (単粒子) / 解像度: 22.0 Å EMDB-3430: Electron cryo-microscopy of human P-glycoprotein: ADP bound state - open conformation #3 手法: EM (単粒子) / 解像度: 22.0 Å
由来	Homo sapiens (ヒト) Mus musculus (ハツカネズミ)