Alanine, Serine, Cysteine-preferring Transporter 2 (SLC1A5) (SLC1A5)

L-glutamine binding sites refer to the specific structural pockets on proteins that interact with the amino acid L-glutamine, a critical nutrient for cellular metabolism and growth. In human physiology and drug discovery, this term most frequently refers to the active sites of high-affinity glutamine transporters, particularly the Alanine, Serine, Cysteine-preferring Transporter 2 (SLC1A5/ASCT2), and enzymes like Glutaminase (GLS). SLC1A5 is a major transporter that cancer cells often overexpress to meet their increased demand for glutamine, which fuels the TCA cycle and supports macromolecular synthesis. Inhibiting these binding sites with small molecules, such as the competitive inhibitor V-9302, can disrupt cancer cell metabolism, induce oxidative stress, and lead to cell death. Additionally, bacterial glutamine-binding proteins (GlnH) are studied as targets for antimicrobial vaccines and biosensors due to their essential role in bacterial nutrient acquisition. Targeting these sites represents a significant strategy in oncology and infectious disease, although maintaining normal amino acid homeostasis in healthy tissues remains a therapeutic challenge.

Other names

ASCT2Neutral amino acid transporter ASCT2L-glutamine transporterATB(0)M7V1AAATGlutamine-binding protein (GlnH)Glutaminase (GLS) active site

Competitive inhibition of glutamine transport, Allosteric inhibition of glutaminase, Substrate supplementation