6bmi | pdb_00006bmi

Crystal Structure of GltPh R397C in complex with L-Serine

spinqualitylabelsall models 6bmi, resolution 3.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6bmi is a 3 chain structure with sequence from Pyrococcus horikoshii OT3. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.9Å Ligands: NA, SER Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GLT_PYRHO Sodium-dependent, high-affinity amino acid transporter that mediates aspartate uptake (PubMed:17435767, PubMed:19380583, PubMed:17230192, Ref.11). Has only very low glutamate transport activity (PubMed:19380583, PubMed:17230192). Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions, resulting in electrogenic transport (PubMed:17435767, PubMed:19380583, Ref.11). Na(+) binding enhances the affinity for aspartate (PubMed:19380583, Ref.11). Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport (PubMed:17435767). In contrast to mammalian homologs, transport does not depend on pH or K(+) ions (PubMed:19380583). [PDB:4P19] Publication Abstract from PubMed 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. Structural characterisation reveals insights into substrate recognition by the glutamine transporter ASCT2/SLC1A5.,Scopelliti AJ, Font J, Vandenberg RJ, Boudker O, Ryan RM Nat Commun. 2018 Jan 2;9(1):38. doi: 10.1038/s41467-017-02444-w. PMID:29295993 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Symporter 3D structures

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