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| | ==Crystal Structure of GltPh R397C in complex with L-Cysteine== | | ==Crystal Structure of GltPh R397C in complex with L-Cysteine== |
| - | <StructureSection load='6bau' size='340' side='right' caption='[[6bau]], [[Resolution|resolution]] 3.80Å' scene=''> | + | <StructureSection load='6bau' size='340' side='right'caption='[[6bau]], [[Resolution|resolution]] 3.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6bau]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BAU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BAU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6bau]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Pyrococcus_horikoshii_OT3 Pyrococcus horikoshii OT3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BAU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BAU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CYS:CYSTEINE'>CYS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2nwx|2nwx]], [[6bat|6bat]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CYS:CYSTEINE'>CYS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6bau FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bau OCA], [http://pdbe.org/6bau PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bau RCSB], [http://www.ebi.ac.uk/pdbsum/6bau PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bau ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6bau FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bau OCA], [https://pdbe.org/6bau PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bau RCSB], [https://www.ebi.ac.uk/pdbsum/6bau PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bau ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GLT_PYRHO 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).<ref>PMID:17230192</ref> <ref>PMID:17435767</ref> <ref>PMID:19380583</ref> [PDB:4P19] | + | [https://www.uniprot.org/uniprot/GLT_PYRHO 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).<ref>PMID:17230192</ref> <ref>PMID:17435767</ref> <ref>PMID:19380583</ref> [PDB:4P19] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6bau" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6bau" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Symporter 3D structures|Symporter 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Boudker, O]] | + | [[Category: Large Structures]] |
| - | [[Category: Font, J]] | + | [[Category: Pyrococcus horikoshii OT3]] |
| - | [[Category: Ryan, R M]] | + | [[Category: Boudker O]] |
| - | [[Category: Scopelliti, A J]] | + | [[Category: Font J]] |
| - | [[Category: Vandenberg, R J]] | + | [[Category: Ryan RM]] |
| - | [[Category: Amino acid transporter transmembrane transporter aspartate transporter]] | + | [[Category: Scopelliti AJ]] |
| - | [[Category: Transport protein]] | + | [[Category: Vandenberg RJ]] |
| Structural highlights
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).[1] [2] [3] [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[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Boudker O, Ryan RM, Yernool D, Shimamoto K, Gouaux E. Coupling substrate and ion binding to extracellular gate of a sodium-dependent aspartate transporter. Nature. 2007 Jan 25;445(7126):387-93. Epub 2007 Jan 17. PMID:17230192 doi:10.1038/nature05455
- ↑ Ryan RM, Mindell JA. The uncoupled chloride conductance of a bacterial glutamate transporter homolog. Nat Struct Mol Biol. 2007 May;14(5):365-71. doi: 10.1038/nsmb1230. Epub 2007 Apr , 15. PMID:17435767 doi:http://dx.doi.org/10.1038/nsmb1230
- ↑ Ryan RM, Compton EL, Mindell JA. Functional characterization of a Na+-dependent aspartate transporter from Pyrococcus horikoshii. J Biol Chem. 2009 Jun 26;284(26):17540-8. doi: 10.1074/jbc.M109.005926. Epub 2009, Apr 20. PMID:19380583 doi:http://dx.doi.org/10.1074/jbc.M109.005926
- ↑ Scopelliti AJ, Font J, Vandenberg RJ, Boudker O, Ryan RM. Structural characterisation reveals insights into substrate recognition by the glutamine transporter ASCT2/SLC1A5. Nat Commun. 2018 Jan 2;9(1):38. doi: 10.1038/s41467-017-02444-w. PMID:29295993 doi:http://dx.doi.org/10.1038/s41467-017-02444-w
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