6v8g | pdb_00006v8g

GltPh mutant - Y204L A345V V366A

spinqualitylabelsall models 6v8g, resolution 3.38Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6v8g 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 3.38Å Ligands: ASP, NA 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 Membrane transporters mediate cellular uptake of nutrients, signaling molecules, and drugs. Their overall mechanisms are often well understood, but the structural features setting their rates are mostly unknown. Earlier single-molecule fluorescence imaging of the archaeal model glutamate transporter homologue GltPh from Pyrococcus horikoshii suggested that the slow conformational transition from the outward- to the inward-facing state, when the bound substrate is translocated from the extracellular to the cytoplasmic side of the membrane, is rate limiting to transport. Here, we provide insight into the structure of the high-energy transition state of GltPh that limits the rate of the substrate translocation process. Using bioinformatics, we identified GltPh gain-of-function mutations in the flexible helical hairpin domain HP2 and applied linear free energy relationship analysis to infer that the transition state structurally resembles the inward-facing conformation. Based on these analyses, we propose an approach to search for allosteric modulators for transporters. The high-energy transition state of the glutamate transporter homologue GltPh.,Huysmans GHM, Ciftci D, Wang X, Blanchard SC, Boudker O EMBO J. 2021 Jan 4;40(1):e105415. doi: 10.15252/embj.2020105415. Epub 2020 Nov, 13. PMID:33185289 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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