Crystal Structure Analysis of LeuT complexed with L-leucine, sodium and desipramine

Beta-Octylglucoside; octyl beta-D-glucoside; octyl D-glucoside; octyl glucoside

Antidepressant binding site in a bacterial homologue of neurotransmitter transporters.

Crystal structure of a bacterial homologue of Na+/Cl--dependent neurotransmitter transporters

MEVKREHWATRLGLILAMAGNAVGLGNFLRFPVQAAENGGGAFMIPYIIAFLLVGIPLMWIEWAMGRYGGAQGHGTTPAI
FYLLWRNRFAKILGVFGLWIPLVVAIYYVYIESWTLGFAIKFLVGLVPEPPPNATDPDSILRPFKEFLYSYIGVPKGDEP
ILKPSLFAYIVFLITMFINVSILIRGISKGIERFAKIAMPTLFILAVFLVIRVFLLETPNGTAADGLNFLWTPDFEKLKD
PGVWIAAVGQIFFTLSLGFGAIITYASYVRKDQDIVLSGLTAATLNEKAEVILGGSISIPAAVAFFGVANAVAIAKAGAF
NLGFITLPAIFSQTAGGTFLGFLWFFLLFFAGLTSSIAIMQPMIAFLEDELKLSRKHAVLWTAAIVFFSAHLVMFLNKSL
DEMDFWAGTIGVVFFGLTELIIFFWIFGADKAWEEINRGGIIKVPRIYYYVMRYITPAFLAVLLVVWAREYIPKIMEETH
WTVWITRFYIIGLFLFLTFLVFLAERRRNHESAGTLVPR

17-22% PEGMME 550, 200 mM NaCl, 100 mM HEPES-NaOH, pH 7.0, VAPOR DIFFUSION, HANGING DROP, temperature 293K

same protein complexed with L-leucine and sodium

same protein complexed with L-leucine, sodium, and clomipramine

same protein complexed with L-leucine, sodium, and imipramine

The same protein complexed with L-alanine, clomipramine and sodium

BIOMOLECULE: 1

The biological assembly might not be physiologically relevant mainly because of the results authors obtained in solution. The actual residues in the relevant transmembrane domains (TM9 and TM12) are not conserved in the eukaryotic homologues. Authors are not 100% sure because crosslinking the protein in a lipid bilayer has not been performed.

HETEROGEN

The authors state that C2 numbering is in crystallographic notation and it is the same as C3 numbering in IUPAC. Regarding the bond order difference for the C5-C6 bond, the authors used the topology and parameter files derived from the small molecule crystal structures of clomipramine and imipramine rather than theoretical values.

Structure in asymmetric unit starts at R5 because of disorder. Residues E129, T515, and L516 are modeled as alanines because of disorder. Residues N133, A134, V517, P518, and R519 are not modeled because of disorder. C-terminal residues GTL modeled as GAA because of disorder.

The biological unit is the monomer, which is the asymmetric unit.

membrane protein, neurotransmitter sodium symporter, occluded, secondary amine tricyclic antidepressant, dibenzazepine, Transmembrane, Transport, TRANSPORT PROTEIN

MEVKREHWATRLGLILAMAGNAVGLGNFLRFPVQAAENGGGAFMIPYIIAFLLVGIPLMWIEWAMGRYGGAQGHGTTPAI
FYLLWRNRFAKILGVFGLWIPLVVAIYYVYIESWTLGFAIKFLVGLVPEPPPNATDPDSILRPFKEFLYSYIGVPKGDEP
ILKPSLFAYIVFLITMFINVSILIRGISKGIERFAKIAMPTLFILAVFLVIRVFLLETPNGTAADGLNFLWTPDFEKLKD
PGVWIAAVGQIFFTLSLGFGAIITYASYVRKDQDIVLSGLTAATLNEKAEVILGGSISIPAAVAFFGVANAVAIAKAGAF
NLGFITLPAIFSQTAGGTFLGFLWFFLLFFAGLTSSIAIMQPMIAFLEDELKLSRKHAVLWTAAIVFFSAHLVMFLNKSL
DEMDFWAGTIGVVFFGLTELIIFFWIFGADKAWEEINRGGIIKVPRIYYYVMRYITPAFLAVLLVVWAREYIPKIMEETH
WTVWITRFYIIGLFLFLTFLVFLAERRRNHESA