Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural basis for substrate and inhibitor recognition of human multidrug transporter MRP4.
Journal, issue, pages	Commun Biol, Vol. 6, Issue 1, Page 549, Year 2023
Publish date	May 22, 2023
Authors	Ying Huang / Chenyang Xue / Liangdong Wang / Ruiqian Bu / Jianqiang Mu / Yong Wang / Zhongmin Liu /
PubMed Abstract	Human multidrug resistance protein 4 (hMRP4, also known as ABCC4), with a representative topology of the MRP subfamily, translocates various substrates across the membrane and contributes to the ...Human multidrug resistance protein 4 (hMRP4, also known as ABCC4), with a representative topology of the MRP subfamily, translocates various substrates across the membrane and contributes to the development of multidrug resistance. However, the underlying transport mechanism of hMRP4 remains unclear due to a lack of high-resolution structures. Here, we use cryogenic electron microscopy (cryo-EM) to resolve its near-atomic structures in the apo inward-open and the ATP-bound outward-open states. We also capture the PGE1 substrate-bound structure and, importantly, the inhibitor-bound structure of hMRP4 in complex with sulindac, revealing that substrate and inhibitor compete for the same hydrophobic binding pocket although with different binding modes. Moreover, our cryo-EM structures, together with molecular dynamics simulations and biochemical assay, shed light on the structural basis of the substrate transport and inhibition mechanism, with implications for the development of hMRP4-targeted drugs.
External links	Commun Biol / PubMed:37217525 / PubMed Central
Methods	EM (single particle)
Resolution	2.95 - 3.8 Å
Structure data	35834 8iz7 EMDB-35834, PDB-8iz7: cryo-EM structure of sulindac-bound hMRP4 Method: EM (single particle) / Resolution: 3.8 Å 35835 8iz8 EMDB-35835, PDB-8iz8: cryo EM structure of apo hMRP4 Method: EM (single particle) / Resolution: 3.13 Å 35836 8iz9 EMDB-35836, PDB-8iz9: cryo-EM structure of PGE1-bound hMRP4 Method: EM (single particle) / Resolution: 2.95 Å 35837 8iza EMDB-35837, PDB-8iza: cryo-EM structure of ATP-bound hMRP4 Method: EM (single particle) / Resolution: 3.48 Å
Chemicals	ChemComp-SUZ: [(1Z)-5-fluoro-2-methyl-1-{4-[methylsulfinyl]benzylidene}-1H-inden-3-yl]acetic acid / antiinflammatoryYM ChemComp-XPG: 7-[(1R,3R)-3-hydroxy-2-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-5-oxocyclopentyl]heptanoic acid / medicationYM ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying moleculeYM ChemComp-MG*: Unknown entry
Source	homo sapiens (human)
Keywords	MEMBRANE PROTEIN / cryo-EM structure of sulindac-bound hMRP4 / cryo EM structure of apo hMRP4 / cryo-EM structure of PGE1-bound hMRP4 / ATP-bound hMRP4