Low-mode docking search in iGluR homology models implicates three residues in the control of ligand selectivity.
Homology models of the ionotropic rat kainate receptor iGluR6, based on the ligand binding domains of iGluR2, were constructed. A systematic analysis by low-mode docking searches of kainic acid in homology models of the native iGluR6 receptor, chimeric (iGluR2 and iGluR6) receptors and mutant receptors have identified three residues which influence the conformation of kainic acid in the binding core and hence the affinity for kainic acid. These residues are Leu650, Thr649 and Leu704, all located in domain 2. Leu650 has previously been implicated in the control of selectivity of iGluR2. However, this is the first report that suggests that Thr649 and Leu704 play a role in receptor selectivity.
Department of Chemistry and Biochemistry, Florida International University, 11200 SW 8th St., Miami, FL 33199, USA.
Jonierr
J
Rodriguez
Luis
L
Carcache
Kathleen S
KS
Rein
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D004252:DNA Mutational Analysis; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology*; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D011485:Protein Binding; D051381:Rats; D018091:Receptors, AMPA / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D000097806:GluK2 Kainate Receptor
D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid; D008024:Ligands; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor; C104722:glutamate receptor ionotropic, AMPA 2