Drug Transport and Resistance Mechanisms

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.

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

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.

This study identifies nine novel P-gp inhibitors using a computationally accelerated drug discovery pipeline, showing they reverse multidrug resistance in cancer cells with minimal toxicity to non-cancerous cells.

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

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

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.

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

The paper determines the cryo-EM structure of Ycf1 bound to oxidized glutathione and identifies a 'flex-pocket' mechanism for substrate binding and specificity.

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

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.

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

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

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

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

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.

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 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 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.

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

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.

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

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

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

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.

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

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

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

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.