6BAT

Crystal Structure of Wild-Type GltPh in complex with L-aspartate

Summary for 6BAT

• Entry DOI: 10.2210/pdb6bat/pdb
• Related: 2NWX
• Descriptor: Glutamate transporter homolog, SODIUM ION, ASPARTIC ACID (3 entities in total)
• Functional Keywords: amino acid transporter transmembrane transporter aspartate transporter, transport protein
• Biological source: Pyrococcus horikoshii
• Total number of polymer chains: 3
• Total formula weight: 133469.39

Authors

Font, J.,Scopelliti, A.J.,Vandenberg, R.J.,Boudker, O.,Ryan, R.M. (deposition date: 2017-10-15, release date: 2018-01-17, Last modification date: 2023-10-04)

Primary citation

Scopelliti, A.J.,Font, J.,Vandenberg, R.J.,Boudker, O.,Ryan, R.M.
Structural characterisation reveals insights into substrate recognition by the glutamine transporter ASCT2/SLC1A5.
Nat Commun, 9:38-38, 2018

PubMed Abstract: Cancer cells undergo a shift in metabolism where they become reliant on nutrients such as the amino-acid glutamine. Glutamine enters the cell via the alanine/serine/cysteine transporter 2 (ASCT2) that is upregulated in several cancers to maintain an increased supply of this nutrient and are therefore an attractive target in cancer therapeutic development. ASCT2 belongs to the glutamate transporter (SLC1A) family but is the only transporter in this family able to transport glutamine. The structural basis for glutamine selectivity of ASCT2 is unknown. Here, we identify two amino-acid residues in the substrate-binding site that are responsible for conferring glutamine selectivity. We introduce corresponding mutations into a prokaryotic homologue of ASCT2 and solve four crystal structures, which reveal the structural basis for neutral amino acid and inhibitor binding in this family. This structural model of ASCT2 may provide a basis for future development of selective ASCT2 inhibitors to treat glutamine-dependent cancers.

PubMed: 29295993
DOI: 10.1038/s41467-017-02444-w

Experimental method

X-RAY DIFFRACTION (3.4 Å)