How Cryo-EM Has Expanded Our Understanding of Membrane Transporters.

Drug Metab Dispos

Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee

Published: August 2023

AI Article Synopsis

  • Over the last 20 years, advancements in membrane protein studies have shed light on how transporters function to move various substances across membranes.
  • The flexibility of ligand binding pockets in these proteins, which allows them to accommodate different substrates, complicates drug development efforts.
  • The paper specifically reviews five important transporters (ABCB1, ABCC1, ABCG2, SLC19A1, SLC29A1) linked to diseases and drug resistance, emphasizing their structure, function, and interaction with drugs in relation to chemotherapy outcomes.

Article Abstract

Over the past two decades, technological advances in membrane protein structural biology have provided insight into the molecular mechanisms that transporters use to move diverse substrates across the membrane. However, the plasticity of these proteins' ligand binding pockets, which allows them to bind a range of substrates, also poses a challenge for drug development. Here we highlight the structure, function, and transport mechanism of ATP-binding cassette/solute carrier transporters that are related to several diseases and multidrug resistance: ABCB1, ABCC1, ABCG2, SLC19A1, and SLC29A1. SIGNIFICANCE STATEMENT: ATP-binding cassette transporters and solute carriers play vital roles in clinical chemotherapeutic outcomes. This paper describes the current understanding of the structure of five pharmacologically relevant transporters and how they interact with their ligands.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10353158PMC
http://dx.doi.org/10.1124/dmd.122.001004DOI Listing

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