Drug Transport and Resistance Mechanisms

Cryo-electron microscopy structures of a zinc uptake ABC transporter

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.

The functional plasticity of the YhdWXYZ ABC transporter enables antibiotic homeostasis and host colonisation in enteric bacteria

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

Capturing transient states of heterodimeric ABC transporter TM287/288 by Time-Resolved Small-Angle X-ray Scattering

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.

Inhibition of PTCH1 drug efflux activity enhances chemotherapy efficacy against triple negative breast cancer

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.

Structural basis of drug efflux by the staphylococcal efflux pump QacA

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

Structural and cellular insights into the inhibition of the drug efflux activity of the HEDGEHOG receptor PATCHED1

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.

A dual sensor regulates P-glycoproteins structural plasticity

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.

An Investigation of the Conformational Dynamics of ABC Exporter PCAT1 using Microsecond-Level MD Simulations

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

ABCC1 protects skin dendritic cells from FITC-induced toxicity by efflux and extracellular glutathione buffering

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

Miniprotein inhibitors of the Staphylococcus aureus efflux transporter NorA

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.

Dicloxacillin and flucloxacillin inhibit hepatic uptake transporters - in vitro investigations and physiological based pharmacokinetic modelling

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

Allosteric effects of the coupling cation in melibiose transporter MelB

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.

A Cationic Amphiphilic Drug (CAD) Defense System in the Nematode Caenorhabditis elegans

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.

Energetic and structural control of polyspecificity in a multidrug transporter

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

Molecular mechanism of substrate transport by human peroxisomal ABCD3

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.

Cryo-EM reveals the structural heterogeneity and conformational flexibility of multidrug efflux pumps MdtB and MdtF

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

Outward-facing P-glycoprotein bound to drug displays nucleotide-dependent drug egress mechanism

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.

Drug-bound P-glycoprotein reveals nucleotide-dependent ligand pockets and ingress channels

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

Molecular basis for multidrug efflux by an anaerobic RND transporter

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.

Single-molecule dynamics reveal ATP binding alone powers substrate translocation by an ABC transporter

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

Bidirectional communication between nucleotide and substrate binding sites in a type IV multidrug ABC transporter

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.

BRG1 targeting overcomes ABCC-based multidrug resistance induced by paclitaxel

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.

BC-Predict Database: A Curated Resource of Experimentally Validated Markers in Multidrug Resistance in Breast Cancer

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.

Mechanistic Insights into the Structural Asymmetry of the LanFEG Transporter NisFEG in Lantibiotic Immunity

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.

Selective Agonism of Liver and Gut FXR Prevents Cholestasis and Intestinal Atrophy in Parenterally Fed Neonatal Pigs

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.

Overcoming rapaprotin resistance through inhibition of P-glycoprotein

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.

MDR1 promotes CD8 T cell persistence in tumors and protects against cytotoxic chemotherapy

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

Cryo-EM of ATP-driven dynamics and itraconazole binding of the fungal drug efflux ABC pump Candida glabrata Cdr1

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

Insights into the linker domain in ABCB1/P-glycoprotein

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.

GLUCURONIDATION: THE LAST DEFENSIVE LINE AGAINST BILEACID TOXICITY DURING CHOLESTASIS.

This study evaluates glucuronidation's role in protecting liver cells during cholestatic conditions by analyzing BA-G accumulation and UGT enzyme expression in response to bile acids and their agonists.