5jag | pdb_00005jag

LeuT T354H mutant in the outward-oriented, Na+-free Return State

spinqualitylabelsall models 5jag, resolution 2.58Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5jag is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BOG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Publication Abstract from PubMed Bacterial members of the neurotransmitter:sodium symporter (NSS) family perform Na(+)-dependent amino-acid uptake and extrude H(+) in return. Previous NSS structures represent intermediates of Na(+)/substrate binding or intracellular release, but not the inward-to-outward return transition. Here we report crystal structures of Aquifex aeolicus LeuT in an outward-oriented, Na(+)- and substrate-free state likely to be H(+)-occluded. We find a remarkable rotation of the conserved Leu25 into the empty substrate-binding pocket and rearrangements of the empty Na(+) sites. Mutational studies of the equivalent Leu99 in the human serotonin transporter show a critical role of this residue on the transport rate. Molecular dynamics simulations show that extracellular Na(+) is blocked unless Leu25 is rotated out of the substrate-binding pocket. We propose that Leu25 facilitates the inward-to-outward transition by compensating a Na(+)- and substrate-free state and acts as the gatekeeper for Na(+) binding that prevents leak in inward-outward return transitions. A conserved leucine occupies the empty substrate site of LeuT in the Na(+)-free return state.,Malinauskaite L, Said S, Sahin C, Grouleff J, Shahsavar A, Bjerregaard H, Noer P, Severinsen K, Boesen T, Schiott B, Sinning S, Nissen P Nat Commun. 2016 May 25;7:11673. doi: 10.1038/ncomms11673. PMID:27221344 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA