Related Experiment Video
Updated: Aug 16, 2025

Characterization of Membrane Transporters by Heterologous Expression in E. coli and Production of Membrane Vesicles
Published on: December 31, 2019
Alanine serine cysteine transporter (ASCT) substrate binding site properties probed with hydroxyhomoserine esters
Elias Ndaru1, Laura Zielewicz1, Yueyue Shi1
1Department of Chemistry, Binghamton University, Binghamton, NY 13902.
Abstract:
The glutamine transporter ASCT2 is highly overexpressed in cancer cells. Block of glutamine uptake by ASCT2 is a potential strategy to inhibit growth of cancer cells. However, pharmacology of the ASCT2 binding site is not well established. In this work, we report the computational docking to the binding site, and the synthesis of a new class of ASCT2 inhibitors based on the novel L-hydroxyhomoserine scaffold. While these compounds inhibit the ASCT2 leak anion conductance, as expected for competitive inhibitors, they did not block leak conductance in glutamate transporters (EAAT1-3 and EAAT5). They were also ineffective with respect to subtype ASCT1, which has >57% amino acid sequence similarity to ASCT2. Molecular docking studies agree very well with the experimental results and suggest specific polar interactions in the ASCT2 binding site. Our findings add to the repertoire of ASCT2 inhibitors and will aid in further studies of ASCT2 pharmacology.
More Related Videos
08:53Biochemical and Structural Characterization of the Carbohydrate Transport Substrate-binding-protein SP0092
Published on: October 2, 2017
12:21Thermostabilization, Expression, Purification, and Crystallization of the Human Serotonin Transporter Bound to S-citalopram
Published on: November 27, 2016
Related Concept Videos
Allosteric Proteins-ATCase
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Ligand Binding and Linkage
Ligand Binding Sites
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...
Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration
Basicity of Heterocyclic Aromatic Amines
¹H NMR Chemical Shift Equivalence: Homotopic and Heterotopic Protons