3gjc

Crystal Structure of the E290S mutant of LeuT with bound OG

spinqualitylabelsall models 3gjc, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3gjc is a 2 chain structure with sequence from "aquifex_aeolicus"_huber_and_stetter_2001 "aquifex aeolicus" huber and stetter 2001. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BOG, LEU, NA Related: 3gjd Gene: aq_2077, snf ("Aquifex aeolicus" Huber and Stetter 2001) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The first crystal structure of the neurotransmitter/sodium symporter homolog LeuT revealed an occluded binding pocket containing leucine and 2 Na(+); later structures showed tricyclic antidepressants (TCAs) in an extracellular vestibule approximately 11 A above the bound leucine and 2 Na(+). We recently found this region to be a second binding (S2) site and that binding of substrate to this site triggers Na(+)-coupled substrate symport. Here, we show a profound inhibitory effect of n-octyl-beta-d-glucopyranoside (OG), the detergent used for LeuT crystallization, on substrate binding to the S2 site. In parallel, we determined at 2.8 A the structure of LeuT-E290S, a mutant that, like LeuT-WT, binds 2 substrate molecules. This structure was similar to that of WT and clearly revealed an OG molecule in the S2 site. We also observed electron density at the S2 site in LeuT-WT crystals, and this also was accounted for by an OG molecule in that site. Computational analyses, based on the available crystal structures of LeuT, indicated the nature of structural arrangements in the extracellular region of LeuT that differentiate the actions of substrates from inhibitors bound in the S2 site. We conclude that the current LeuT crystal structures, all of which have been solved in OG, represent functionally blocked forms of the transporter, whereas a substrate bound in the S2 site will promote a different state that is essential for Na(+)-coupled symport. Binding of an octylglucoside detergent molecule in the second substrate (S2) site of LeuT establishes an inhibitor-bound conformation.,Quick M, Winther AM, Shi L, Nissen P, Weinstein H, Javitch JA Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5563-8. Epub 2009 Mar 23. PMID:19307590 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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