6B7H

Structure of mGluR3 with an agonist

6B7H の概要

• エントリーDOI: 10.2210/pdb6b7h/pdb
• 分子名称: Metabotropic glutamate receptor 3, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: mglur3 glutamate, membrane protein-agonist complex, membrane protein/agonist
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 60220.97

構造登録者

Monn, J.A.,Clawson, D.K. (登録日: 2017-10-04, 公開日: 2018-04-25, 最終更新日: 2024-10-23)

主引用文献

Monn, J.A.,Henry, S.S.,Massey, S.M.,Clawson, D.K.,Chen, Q.,Diseroad, B.A.,Bhardwaj, R.M.,Atwell, S.,Lu, F.,Wang, J.,Russell, M.,Heinz, B.A.,Wang, X.S.,Carter, J.H.,Getman, B.G.,Adragni, K.,Broad, L.M.,Sanger, H.E.,Ursu, D.,Catlow, J.T.,Swanson, S.,Johnson, B.G.,Shaw, D.B.,McKinzie, D.L.,Hao, J.
Synthesis and Pharmacological Characterization of C4beta-Amide-Substituted 2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylates. Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3Receptor Agonist.
J. Med. Chem., 61:2303-2328, 2018

PubMed Abstract: Multiple therapeutic opportunities have been suggested for compounds capable of selective activation of metabotropic glutamate 3 (mGlu) receptors, but small molecule tools are lacking. As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu and mGlu receptor subtypes, a series of C4-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu and mGlu receptor binding affinity and functional cellular responses. From this investigation we identified (1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193), a molecule that demonstrates remarkable mGlu receptor selectivity. Crystallization of 8p with the amino terminal domain of hmGlu revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu receptors in vivo.

PubMed: 29350927
DOI: 10.1021/acs.jmedchem.7b01481

実験手法

X-RAY DIFFRACTION (2.82 Å)