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 and mechanistic basis of substrate transport by the multidrug transporter MRP4.
ジャーナル・号・ページ	Structure, Vol. 31, Issue 11, Page 1407-11418.e6, Year 2023
掲載日	2023年11月2日
著者	Magnus Bloch / Isha Raj / Tillmann Pape / Nicholas M I Taylor /
PubMed 要旨	Multidrug resistance-associated protein 4 (MRP4) is an ATP-binding cassette (ABC) transporter expressed at multiple tissue barriers where it actively extrudes a wide variety of drug compounds. ...Multidrug resistance-associated protein 4 (MRP4) is an ATP-binding cassette (ABC) transporter expressed at multiple tissue barriers where it actively extrudes a wide variety of drug compounds. Overexpression of MRP4 provides resistance to clinically used antineoplastic agents, making it a highly attractive therapeutic target for countering multidrug resistance. Here, we report cryo-EM structures of multiple physiologically relevant states of lipid bilayer-embedded human MRP4, including complexes between MRP4 and two widely used chemotherapeutic agents and a complex between MRP4 and its native substrate. The structures display clear similarities and distinct differences in the coordination of these chemically diverse substrates and, in combination with functional and mutational analysis, reveal molecular details of the transport mechanism. Our study provides key insights into the unusually broad substrate specificity of MRP4 and constitutes an important contribution toward a general understanding of multidrug transporters.
リンク	Structure / PubMed:37683641
手法	EM (単粒子)
解像度	3.0 - 5.5 Å
構造データ	16088 8bjf EMDB-16088, PDB-8bjf: Cryo-EM structure of nanodisc-reconstituted wildtype human MRP4 (inward-facing conformation) 手法: EM (単粒子) / 解像度: 3.0 Å 16292 8bwo EMDB-16292: Cryo-EM structure of nanodisc-reconstituted human MRP4 withE1202Q mutation (outward-facing occluded conformation) PDB-8bwo: Cryo-EM structure of nanodisc-reconstituted human MRP4 with E1202Q mutation (outward-facing occluded conformation) 手法: EM (単粒子) / 解像度: 3.2 Å 16293 8bwp EMDB-16293, PDB-8bwp: Cryo-EM structure of nanodisc-reconstituted wildtype human MRP4 (in complex with methotrexate) 手法: EM (単粒子) / 解像度: 3.6 Å 16294 8bwq EMDB-16294, PDB-8bwq: Cryo-EM structure of nanodisc-reconstituted wildtype human MRP4 (in complex with topotecan) 手法: EM (単粒子) / 解像度: 3.9 Å 16295 8bwr EMDB-16295, PDB-8bwr: Cryo-EM structure of nanodisc-reconstituted wildtype human MRP4 (in complex with prostaglandin E2) 手法: EM (単粒子) / 解像度: 4.0 Å EMDB-16296: Cryo-EM structure of native nanodisc-reconstituted wildtype human MRP4 (inward-facing conformation) - no nucleotides/substrates added 手法: EM (単粒子) / 解像度: 3.3 Å EMDB-16297: Cryo-EM structure of minimal nanodisc-reconstituted wildtype human MRP4 (inward-facing conformation) - no nucleotides/substrates added 手法: EM (単粒子) / 解像度: 5.5 Å
化合物	ChemComp-CLR: CHOLESTEROL / コレステロ-ル ChemComp-Y01: CHOLESTEROL HEMISUCCINATE / コレステリルヘミスクシナ-ト ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP / ATP, エネルギー貯蔵分子YM ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-MTX: METHOTREXATE / メトトレキサ-ト / 化学療法薬YM ChemComp-TTC: (S)-10-[(DIMETHYLAMINO)METHYL]-4-ETHYL-4,9-DIHYDROXY-1H-PYRANO[3',4':6,7]INOLIZINO[1,2-B]-QUINOLINE-3,14(4H,12H)-DIONE / トポテカン / 薬剤, 阻害剤YM ChemComp-P2E: (Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-oxo-cyclopentyl]hept-5-enoic acid / プロスタグランジンE₂ / 薬剤YM
由来	homo sapiens (ヒト)
キーワード	TRANSLOCASE / ABC transporter / ABCC4 / MRP4 / Topotecan bound / PGE2 bound ABC transporter