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Low-mode docking search in iGluR homology models implicates three residues in the control of ligand selectivity

✍ Scribed by Jonierr Rodriguez; Luis Carcache; Kathleen S. Rein


Publisher
John Wiley and Sons
Year
2005
Tongue
English
Weight
123 KB
Volume
18
Category
Article
ISSN
0952-3499

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✦ Synopsis


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.