3F4I

Crystal Structure of LeuT bound to L-selenomethionine and sodium

Summary for 3F4I

• Entry DOI: 10.2210/pdb3f4i/pdb
• Related: 2A65 2QEI 3F3A 3F3C 3F3D 3F3E 3F48 3F4J
• Descriptor: Transporter, SELENOMETHIONINE, octyl beta-D-glucopyranoside, ... (5 entities in total)
• Functional Keywords: membrane protein, slc6, nss, sodium-couple, neurotransmitter, transporter, symport, transmembrane, transport, transport protein
• Biological source: Aquifex aeolicus
• Total number of polymer chains: 1
• Total formula weight: 59781.37

Authors

Singh, S.K.,Piscitelli, C.L.,Yamashita, A.,Gouaux, E. (deposition date: 2008-10-31, release date: 2008-12-23, Last modification date: 2023-11-15)

Primary citation

Singh, S.K.,Piscitelli, C.L.,Yamashita, A.,Gouaux, E.
A competitive inhibitor traps LeuT in an open-to-out conformation.
Science, 322:1655-1661, 2008

PubMed Abstract: Secondary transporters are workhorses of cellular membranes, catalyzing the movement of small molecules and ions across the bilayer and coupling substrate passage to ion gradients. However, the conformational changes that accompany substrate transport, the mechanism by which a substrate moves through the transporter, and principles of competitive inhibition remain unclear. We used crystallographic and functional studies on the leucine transporter (LeuT), a model for neurotransmitter sodium symporters, to show that various amino acid substrates induce the same occluded conformational state and that a competitive inhibitor, tryptophan (Trp), traps LeuT in an open-to-out conformation. In the Trp complex, the extracellular gate residues arginine 30 and aspartic acid 404 define a second weak binding site for substrates or inhibitors as they permeate from the extracellular solution to the primary substrate site, which demonstrates how residues that participate in gating also mediate permeation.

PubMed: 19074341
DOI: 10.1126/science.1166777

Experimental method

X-RAY DIFFRACTION (1.95 Å)