6E5V

human mGlu8 receptor amino terminal domain in complex with (S)-3,4-Dicarboxyphenylglycine (DCPG)

Summary for 6E5V

• Entry DOI: 10.2210/pdb6e5v/pdb
• Descriptor: Metabotropic glutamate receptor 8, 4-[(S)-amino(carboxy)methyl]benzene-1,2-dicarboxylic acid, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: mglur8 atd, grm8, dcpg, signaling protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 118214.70

Authors

Chen, Q.,Ho, J.D.,Ashok, S.,Vargas, M.C.,Wang, J.,Atwell, S.,Bures, M.,Schkeryantz, J.M.,Monn, J.A.,Hao, J. (deposition date: 2018-07-23, release date: 2018-11-07, Last modification date: 2024-11-20)

Primary citation

Chen, Q.,Ho, J.D.,Ashok, S.,Vargas, M.C.,Wang, J.,Atwell, S.,Bures, M.,Schkeryantz, J.M.,Monn, J.A.,Hao, J.
Structural Basis for ( S)-3,4-Dicarboxyphenylglycine (DCPG) As a Potent and Subtype Selective Agonist of the mGlu8Receptor.
J. Med. Chem., 61:10040-10052, 2018

PubMed Abstract: ( S)-3,4-Dicarboxyphenylglycine (DCPG) was first reported in 2001 as a potent orthosteric agonist with high subtype selectivity for the mGlu receptor, but the structural basis for its high selectivity is not well understood. We have solved a cocrystal structure of recombinant human mGlu amino terminal domain (ATD) protein bound to ( S)-DCPG, which possesses the largest lobe opening angle observed to date among known agonist-bound mGlu ATD crystal structures. The binding conformation of ( S)-DCPG observed in the crystal structure is significantly different from that in the homology model built from an l-glutamate-bound rat mGlu ATD crystal structure, which has a smaller lobe opening angle. This highlights the importance of considering various lobe opening angles when modeling mGlu ATD-ligand complex. New homology models of other mGlu receptors based on the ( S)-DCPG-bound mGlu ATD crystal structure were explored to rationalize ( S)-DCPG's high mGlu receptor subtype selectivity.

PubMed: 30365309
DOI: 10.1021/acs.jmedchem.8b01120

Experimental method

X-RAY DIFFRACTION (2.95 Å)