6ODL
Crystal structure of GluN2A agonist binding domain with 4-butyl-(S)-CCG-IV
Summary for 6ODL
| Entry DOI | 10.2210/pdb6odl/pdb |
| Descriptor | Glutamate receptor ionotropic, NMDA 2A,Glutamate receptor ionotropic, NMDA 2A, (1S,2R)-2-[(S)-amino(carboxy)methyl]-1-butylcyclopropane-1-carboxylic acid (3 entities in total) |
| Functional Keywords | nmda receptor, antagonist, transport protein, receptor |
| Biological source | Rattus norvegicus (Rat) More |
| Total number of polymer chains | 2 |
| Total formula weight | 63138.37 |
| Authors | Mou, T.C.,Clausen, R.P.,Sprang, S.R.,Hansen, K.B. (deposition date: 2019-03-26, release date: 2020-04-01, Last modification date: 2024-10-30) |
| Primary citation | Maolanon, A.,Papangelis, A.,Kawiecki, D.,Mou, T.C.,Syrenne, J.T.,Yi, F.,Hansen, K.B.,Clausen, R.P. Stereoselective synthesis of novel 2'-(S)-CCG-IV analogues as potent NMDA receptor agonists. Eur.J.Med.Chem., 212:113099-113099, 2021 Cited by PubMed Abstract: We developed a versatile stereoselective route for the synthesis of new 2'-(S)-CCG-IV analogues. The route allows for late stage diversification and thereby provides access to a great variety of conformationally restricted cyclopropyl glutamate analogues. A selection of the 2'-(S)-CCG-IV analogues were evaluated using two-electrode voltage-clamp electrophysiology at recombinant GluN1/GluN2A-D receptors, demonstrating that agonists can be developed with GluN2 subunit-dependent potency and agonist efficacy. We also describe a crystal structure of the GluN2A agonist binding domain in complex with 2'-butyl-(S)-CCG-IV that determines the position of 2'-substituents in (S)-CCG-IV agonists in the glutamate binding site and provides further insight to the structural determinants of their agonist efficacy. The stereoselective synthesis described here enables versatile and straight-forward modifications to diverse analogues of interest for the development of potent subtype-specific NMDA receptor agonists and other applications. PubMed: 33383257DOI: 10.1016/j.ejmech.2020.113099 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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