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Related Concept Videos

Ligand Binding Sites02:40

Ligand Binding Sites

Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Ligand Binding Sites02:40

Ligand Binding Sites

Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence the...
Drug Binding to Blood Components01:30

Drug Binding to Blood Components

When drugs enter systemic circulation, they interact with various components of the blood, including proteins such as human serum albumin (HSA), α1-acid glycoprotein (AAG), lipoproteins, globulins, and red blood cells (RBCs).
HSA is the most abundant plasma protein and is vital in drug binding. It contains distinct drug-binding sites, with different drugs exhibiting affinity for specific sites. There are three main drug-binding domains for HSA: sites I, II, and III. These domains are further...
Tissue-Drug Binding: Localization of Drugs and its Significance01:24

Tissue-Drug Binding: Localization of Drugs and its Significance

Body tissues, comprising approximately 40% of the body weight, are crucial in drug distribution and localization. These tissues can serve as drug storage sites, competing with plasma binding sites for drug molecules.
Drugs can bind to different tissue components, enhancing their distribution and localization. The factors influencing drug localization in tissues include the drug's lipophilicity, structural characteristics, tissue perfusion rate, and pH differences. These factors determine the...
Drug Distribution: Plasma Protein Binding01:29

Drug Distribution: Plasma Protein Binding

Drugs predominantly attach to plasma proteins, with only a small percentage remaining unbound. The unbound portion can be calculated as one minus the bound fraction. Acidic drugs form large, inactive complexes by reversibly binding to plasma albumin, which prevents them from diffusing across biological barriers. These drug-protein complexes act as reservoirs for the drugs. As the concentration of unbound drugs decreases, these complexes quickly dissociate to release the free drug, maintaining...

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A Bilingual Computational Workflow for Identifying Potential PLK1 Inhibitors in American Sign Language and English
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Substrate and drug binding sites in LeuT.

Ajeeta Nyola1, Nathan K Karpowich, Juan Zhen

  • 1Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, and Department of Cell Biology, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.

Current Opinion in Structural Biology
|August 27, 2010
PubMed
Summary

The leucine transporter (LeuT) structure reveals a secondary binding site that influences substrate release, offering insights into antidepressant drug action on serotonin transporters.

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Real Time Measurements of Membrane Protein:Receptor Interactions Using Surface Plasmon Resonance (SPR)
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Real Time Measurements of Membrane Protein:Receptor Interactions Using Surface Plasmon Resonance (SPR)

Published on: November 29, 2014

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Last Updated: Jun 9, 2026

A Bilingual Computational Workflow for Identifying Potential PLK1 Inhibitors in American Sign Language and English
14:34

A Bilingual Computational Workflow for Identifying Potential PLK1 Inhibitors in American Sign Language and English

Published on: April 3, 2026

Real Time Measurements of Membrane Protein:Receptor Interactions Using Surface Plasmon Resonance (SPR)
09:35

Real Time Measurements of Membrane Protein:Receptor Interactions Using Surface Plasmon Resonance (SPR)

Published on: November 29, 2014

Area of Science:

  • Neuroscience
  • Structural Biology
  • Biochemistry

Background:

  • The neurotransmitter/sodium symporter (NSS) family includes key neuronal transporters for serotonin, norepinephrine, and dopamine.
  • The leucine transporter (LeuT) shares structural homology with these transporters and is inhibited by antidepressants.
  • Previous LeuT crystal structures identified a primary substrate-binding site.

Purpose of the Study:

  • To investigate the structural basis of LeuT inhibition by antidepressants.
  • To elucidate the role of substrate binding sites in transporter mechanism and drug interaction.
  • To provide structural insights into the controversial binding sites of the serotonin transporter.

Main Methods:

  • X-ray crystallography of LeuT-antidepressant complexes.
  • X-ray crystallography of a LeuT-tryptophan complex.
  • Analysis of substrate binding and release mechanisms.

Main Results:

  • Newly determined crystal structures of LeuT-antidepressant complexes offer insights into drug binding.
  • A LeuT-tryptophan complex structure reveals an overlapping binding site with the primary substrate site.
  • Identification of a secondary substrate binding site in LeuT, crucial for primary substrate release.

Conclusions:

  • The two-binding site model of LeuT provides a framework for understanding mammalian transporter inhibition.
  • Structural data on LeuT-antidepressant complexes can inform drug design for serotonin transporter modulation.
  • Understanding LeuT's mechanism aids in deciphering the function and inhibition of related neurotransmitter transporters.