Drug Transport and Resistance Mechanisms

The paper reports cryo-EM structures of the Zn2+ ABC transporter ZnuB-ZnuC from E. coli, revealing a self-regulating mechanism via a zinc sensor.

This study investigates the functional plasticity of the YhdWXYZ ABC transporter in enteric bacteria, showing its role in antibiotic homeostasis and host colonization.

This study captures transient states of the ABC transporter TM287/288 using time-resolved small-angle X-ray scattering and reveals a transient occluded state in its ATP-driven conformational cycle.

This study shows that inhibiting PTCH1 drug efflux improves chemotherapy effectiveness in triple-negative breast cancer cells by increasing drug retention and reducing cell migration.

This study reports crystal structures of the QacA efflux pump in different conformational states, revealing structural dynamics and mechanisms of multidrug transport and extrusion.

The paper investigates the structure of PTCH1 bound to the inhibitor PAH, revealing its mechanism of blocking drug efflux and providing insights for drug design.

The paper uses cryo-EM to study P-glycoprotein in different environments, revealing distinct roles of transmembrane helices 4 and 10 in its functional plasticity.

This study uses microsecond MD simulations and FEP to analyze nucleotide binding and conformational dynamics of PCAT1, revealing Mg2+ and substrate-dependent stabilization mechanisms.

This study identifies ABCC1's role in protecting skin dendritic cells from FITC toxicity through intracellular efflux and extracellular glutathione buffering.

The paper designs miniprotein inhibitors of the Staphylococcus aureus efflux transporter NorA and identifies a promising inhibitor with a cryo-EM structure showing its binding mechanism.

This study investigates how dicloxacillin and flucloxacillin inhibit hepatic and renal transporters in vitro and uses PBPK modeling to assess clinical relevance.

This study investigates the allosteric effects of the coupling cation in the melibiose transporter MelB by integrating structural, HDX-MS, and simulation data to reveal how cation binding enhances sugar-binding affinity through conformational restraint.

This study identifies a CAD defense system in C. elegans involving CYP-35B and PGP-13, showing their roles in CAD metabolism and efflux, and links bacteria to CAD defense activation.

This study investigates how energy and structure control multidrug transporter specificity by analyzing mutations across substrates and energy conditions.

This study determines the cryo-EM structures of human ABCD3 in apo and substrate-bound states, revealing how substrate binding induces ATPase activity and provides structural insights into its transport mechanism.

The paper uses cryo-EM to determine the structures of MdtB and MdtF, revealing structural and functional differences among HAE-RND pumps.

This study uses simulations to reveal how ATP binding and hydrolysis drive drug egress through P-glycoprotein by coordinating transmembrane domain motions and nucleotide states.

This study uses computational analysis to explore how nucleotide states and ligand binding in P-glycoprotein influence drug transport and allosteric signaling.

The paper investigates the molecular mechanism of MdtF, an RND transporter in E. coli, revealing structural and functional adaptations for multidrug efflux under anaerobic and acidic conditions.

The paper uses single-molecule FRET to show ATP binding alone drives peptide translocation by TmrAB without Mg2+.

The paper identifies a conserved residue cluster in BmrA that mediates communication between nucleotide and substrate binding sites in type IV ABC transporters through coupling helix 2.

This study shows that BRG1-based SWI/SNF complex promotes ABCC gene transcription, contributing to paclitaxel resistance, and that targeting BRG1 can overcome this resistance.

The paper develops a curated database of experimentally validated markers for multidrug resistance in breast cancer, identifying key candidates associated with different levels of drug resistance.

This study constructs a full-atom model of the NisFEG transporter in the ATP-bound state, revealing structural asymmetry and interaction mechanisms critical for nisin extrusion and bacterial immunity.

The study shows that enteral OCA prevents cholestasis and intestinal atrophy in neonatal pigs by enhancing bile acid and sterol transport through FXR target genes, with additional intestinal growth benefits.

This study identifies a missense variant in FXR that impairs its conformational transition to an active state, leading to reduced BSEP expression and a PFIC phenotype.

This study identifies P-glycoprotein as a mediator of Rapaprotin resistance and shows that co-treatment with tariquidar restores its efficacy in colorectal cancer cells.

This study shows that MDR1 promotes CD8 T cell persistence in tumors and protects against chemotherapy-induced cell death.

The paper presents cryo-EM structures of the fungal ABC pump Cdr1, revealing its ATP-driven dynamics and drug-binding mechanism.

This study investigates the role of the linker domain in ABCB1/P-glycoprotein using simulations, cryo-EM, and computational methods, revealing its impact on protein structure and function.