4IGR

Crystal structure of the kainate receptor GluK3 ligand-binding domain in complex with the agonist ZA302

4IGR の概要

• エントリーDOI: 10.2210/pdb4igr/pdb
• 関連するPDBエントリー: 3S9E 4IGT
• 分子名称: Glutamate receptor, ionotropic kainate 3, (4R)-4-{3-[hydroxy(methyl)amino]-3-oxopropyl}-L-glutamic acid, POTASSIUM ION, ... (6 entities in total)
• 機能のキーワード: membrane protein, ionotropic glutamate receptor, kainate receptor, ligand-binding domain, agonist
• 由来する生物種: Rattus norvegicus (rat); 詳細
• 細胞内の位置: Cell membrane; Multi-pass membrane protein: P42264
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29549.31

構造登録者

Larsen, A.P.,Venskutonyte, R.,Gajhede, M.,Kastrup, J.S.,Frydenvang, K. (登録日: 2012-12-18, 公開日: 2013-03-06, 最終更新日: 2024-10-30)

主引用文献

Assaf, Z.,Larsen, A.P.,Venskutonyte, R.,Han, L.,Abrahamsen, B.,Nielsen, B.,Gajhede, M.,Kastrup, J.S.,Jensen, A.A.,Pickering, D.S.,Frydenvang, K.,Gefflaut, T.,Bunch, L.
Chemoenzymatic synthesis of new 2,4-syn-functionalized (S)-glutamate analogues and structure-activity relationship studies at ionotropic glutamate receptors and excitatory amino acid transporters.
J.Med.Chem., 56:1614-1628, 2013

PubMed Abstract: In the mammalian central nervous system, (S)-glutamate (Glu) is released from the presynaptic neuron where it activates a plethora of pre- and postsynaptic Glu receptors. The fast acting ionotropic Glu receptors (iGluRs) are ligand gated ion channels and are believed to be involved in a vast number of neurological functions such as memory and learning, synaptic plasticity, and motor function. The synthesis of 14 enantiopure 2,4-syn-Glu analogues 2b-p is accessed by a short and efficient chemoenzymatic approach starting from readily available cyclohexanone 3. Pharmacological characterization at the iGluRs and EAAT1-3 subtypes revealed analogue 2i as a selective GluK1 ligand with low nanomolar affinity. Two X-ray crystal structures of the key analogue 2i in the ligand-binding domain (LBD) of GluA2 and GluK3 were determined. Partial domain closure was seen in the GluA2-LBD complex with 2i comparable to that induced by kainate. In contrast, full domain closure was observed in the GluK3-LBD complex with 2i, similar to that of GluK3-LBD with glutamate bound.

PubMed: 23414088
DOI: 10.1021/jm301433m

実験手法

X-RAY DIFFRACTION (2.65 Å)