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Related Concept Videos

Membrane Transporters01:31

Membrane Transporters

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Transporters are essential membrane transport proteins with functions related to cell nutrition, homeostasis, communication, etc. Approximately 7% of all genes in the human genome code for transporters or transporter-related proteins.
Transporters are mainly composed of alpha-helices, built from bundles of ten or more helices traversing the plasma membrane. The solute-binding sites are located midway, where some of the helices are broken or distorted, making space for the binding site through...
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Drug Absorption Mechanism: Carrier-Mediated Membrane Transport01:19

Drug Absorption Mechanism: Carrier-Mediated Membrane Transport

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Certain large, lipid-insoluble drug molecules that resemble amino acids, peptides, or glucose, require specialized carrier proteins to facilitate their diffusion across cell membranes. This transport can occur through either facilitated diffusion, which does not require energy input, or active transport, which does require energy input.
Facilitated diffusion is a passive process that utilizes human Solute Carrier (SLC) transporters. These transporters bind to the drug, undergo structural...
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Active Transport01:14

Active Transport

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Active transport is a critical biological process that allows cells to move solutes against an electrochemical gradient. This process requires direct energy input and is characterized by its selectivity, saturability, and susceptibility to competitive inhibition.
Primary active transporters, like Na+, K+ and -ATPase, directly utilize ATP to move ions across the membrane. These transporters play significant roles in various physiological processes. For instance, Na+, K+ and -ATPase maintain...
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The Significance of Membrane Transport01:44

The Significance of Membrane Transport

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The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
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ABC Transporters: Exporter01:31

ABC Transporters: Exporter

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ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
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Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

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The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
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Author Spotlight: Expression and Purification of Human Solute Carrier Transporters Using Codon-Optimized Genes
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SLC Transporters: Structure, Function, and Drug Discovery.

Claire Colas1, Peter Man-Un Ung1, Avner Schlessinger2

  • 1Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY 10029.

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Structure-based drug discovery for human Solute Carrier (SLC) transporters is advancing. Computational methods like homology modeling and virtual screening are key to identifying chemical probes for these vital drug targets.

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A Proteoliposome-Based Efflux Assay to Determine Single-molecule Properties of Cl- Channels and Transporters
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Selection of Transporter-Targeted Inhibitory Nanobodies by Solid-Supported-Membrane SSM-Based Electrophysiology
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Area of Science:

  • Biochemistry
  • Pharmacology
  • Structural Biology

Background:

  • Human Solute Carrier (SLC) transporters are crucial drug targets.
  • Understanding their structure, dynamics, and ligand interactions is essential for drug discovery.
  • Recent advances in structural determination and computational power enhance structure-based drug design for SLCs.

Purpose of the Study:

  • To review the structures and transport mechanisms of SLC transporters.
  • To describe computational techniques for discovering chemical probes for SLCs.
  • To illustrate the application of these methods through case studies.

Main Methods:

  • Review of existing literature on SLC transporter structures and mechanisms.
  • Description of computational techniques including homology modeling and virtual screening.
  • Case study analysis integrating computational and experimental data.

Main Results:

  • Overview of diverse SLC transporter structures and transport mechanisms.
  • Demonstration of computational tools for identifying chemical probes.
  • Successful characterization of nutrient and metabolite transporters (LAT-1, ASCT2, SLC13 family, GLUT1) using integrated approaches.

Conclusions:

  • Computational methods are increasingly vital for structure-based drug discovery of human SLCs.
  • Integration of computation and experiment accelerates the characterization of SLC transporters.
  • Future directions focus on leveraging these methods for the broad human SLC superfamily.