Drug Transport and Resistance Mechanisms

Crosstalk between CD8+ T cells and systemic bile acid metabolism controls LCMV-induced immunopathology

This study shows that CD8+ T cells and bile acid metabolism interact during LCMV infection, with bile acids affecting T cell responses and immunopathology.

Selected plasma-associated molecular species remodel the ABCB1 linker with effects retained under structure-derived tethering

The paper uses molecular dynamics simulations to study how plasma-associated species affect the conformational behavior of the ABCB1 linker, identifying persistent and motion-dependent responses.

Beyond Gatekeeping: Efflux Pumps Remotely Destabilize Cytoplasmic Drug-Target Interactions by Limiting Rebinding.

The paper shows efflux pumps reduce drug-target binding affinity by limiting rebinding, not just by reducing drug entry, thereby enhancing multidrug resistance.

Membrane Transport of Rhodamine 6G by the reconstituted multidrug resistance ABC transporter Pdr5 in Horizontal Lipid Bilayer

This study investigates how reconstituted Pdr5 transporter moves Rhodamine 6G across a lipid bilayer using ATP, showing active transport of the cation.

A physiologically-based model of bile acid metabolism in humans

The paper develops a physiologically-based model of bile acid metabolism in humans to analyze how disease-related changes affect bile acid composition along the gut-liver-axis.

Structure and Post-Translational Modification of the Prostaglandin Transporter

This paper determines the cryo-EM structure of human PGT and identifies disulfide bonds critical for its function and post-translational modifications.

Two stages of substrate discrimination dictate selectivity in the E. coli MetNI-Q ABC transporter system

A versatile method to expand and compare transporter substrate spectra

The paper introduces an untargeted method to expand and compare substrate spectra of plant transporters using metabolite accumulation patterns in Xenopus laevis oocytes.

The C-terminus of the multi-drug efflux pump EmrE prevents proton leak by gating transport

This paper shows that the C-terminal tail of EmrE prevents proton leak by acting as a secondary gate, which is unlocked by substrate binding.

Structure and iron-transporting mechanism of brain organic cation transporter 1

This study determines the structure of mouse BOCT1 and reveals its function as an independent iron transporter using cryo-EM and functional assays.

Identification of antibody-drug conjugate payloads which are substrates of ATP-binding cassette drug efflux transporters

This study identifies ADC payloads transported by ABC transporters, showing potential for drug resistance and suggesting payload selection to avoid this.

From discovery to translation: Endogenous substrates of OAT1 and OAT3 as clinical biomarkers for renal secretory function

This paper identifies 23 endogenous substrates of OAT1/3 as clinical biomarkers for renal secretory function, enabling prediction of drug interactions and interindividual variability.

Antibiotic-Specific Conformational Landscapes of a Multidrug Transporter

This study uses smFRET to analyze conformational dynamics of LmrP, revealing antibiotic-dependent heterogeneity in its conformational landscape and interconversion kinetics.

Structure of YbbAP-TesA: a Type VII ABC transporter lipid-hydrolase complex

The paper describes the structure and function of the YbbAP-TesA complex, a Type VII ABC transporter lipid-hydrolase in E. coli, revealing its role in substrate extraction and hydrolysis.

Molecular mechanism of thyroxine transport by monocarboxylate transporters

This study determines the structures of MCT8 and MCT10 in different states to elucidate the molecular mechanism of thyroid hormone transport and explain disease-related mutations.

The solute carrier superfamily interactome

The paper maps protein-protein interactions of 396 SLC transporters using interaction proteomics and functional assays, providing a resource for understanding SLC function and drug targeting.

The genetic interaction map of the human solute carrier superfamily

The paper systematically identifies genetic interactions among human solute carrier proteins using CRISPR-Cas12a and -Cas9, revealing 1,236 interactions with growth phenotypes and highlighting SLC39A1's role in metabolic reprogramming.

Metabolic mapping of the human solute carrier superfamily

The paper systematically evaluates the metabolic and transcriptional effects of SLC superfamily members, identifying new substrates and functional groups.

A key residue of the extracellular gate provides quality control contributing to ABCG substrate specificity

The paper shows that mutation of L704 in ABCG36 affects substrate specificity by altering transport of IBA and CLX, with molecular dynamics supporting a quality control role.

Overcoming acquired doxorubicin resistance of ovarian carcinoma cells by verapamil-mediated promotion of DNA damage-driven cell death

This study identifies verapamil as a synergistic agent to overcome doxorubicin resistance in ovarian cancer cells by enhancing DNA damage and apoptosis.

A structural and mechanistic model for BSEP dysfunction in PFIC2 cholestatic disease

This study investigates how BSEP mutations cause PFIC2 by analyzing protein stability and structure, identifying a key interface affected by disease-causing variants.

Structure and inhibition mechanisms of Mycobacterium tuberculosis essential transporterefflux protein A

This study identifies two inhibitors of the Mtb efflux pump EfpA, determines their binding mechanisms, and suggests their potential for combination anti-tuberculosis therapy.

Human jejunal enteroids for studies of epithelial drug transport and metabolism

This study establishes and characterizes human jejunal enteroids for studying epithelial drug transport and metabolism, showing they recapitulate in vivo features and accurately predict drug pharmacokinetics.

Quantitative contributions of hepatic and renal organic cation transporters to the clinical pharmacokinetic cimetidine-metformin interaction

This study investigates how cimetidine affects metformin's pharmacokinetics by inhibiting OCT1 and OCT2, showing increased plasma exposure and reduced renal clearance.

Structural basis of phosphate export by human XPR1

This study determines the closed and open structures of human XPR1, revealing its phosphate export mechanism and potential therapeutic implications.

Lipid-mediated mechanism of drug extrusion by a heterodimeric ABC exporter

This study reveals how lipid competition modulates drug affinity in ABC exporters through structural and simulation analyses of BmrCD.

Functional Proteomics of ABC Importers Reveal Synchronization of Mechanisms, Cellular Abundances, and Counterintuitive Stoichiometries

The paper develops a proteomic approach to study E. coli ABC importers, revealing abundance variations, inverse correlations between substrate-binding protein affinities and permease interactions, and counterintuitive stoichiometries.

Influence of Gut Microbiota on Oral Drug Absorption and Metabolism

This study shows gut microbiota affects drug absorption and metabolism by altering gene expression and intestinal permeability in mice.

Specificity and tunability of efflux pumps: a new role for the proton gradient?

This study shows that efflux pump specificity is influenced by proton gradient and membrane potential, offering new strategies to combat bacterial resistance.

Proximal Tubule-on-Chip for Predicting Cation Transport: Dynamic Insights into Drug Transporter Expression and Function

This study develops a proximal tubule-on-chip model to investigate dynamic drug transporter expression and function, showing flow exposure modulates mRNA expression and enhances cell polarization.