4Q30: Nitrowillardiine Bound To The Ligand Binding Domain Of Glua2 At Ph 3.5

Citation:
Abstract
Understanding the thermodynamics of binding of a lead compound to a receptor can provide valuable information for drug design. The binding of compounds, particularly partial agonists, to subtypes of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor is, in some cases, driven by increases in entropy. Using a series of partial agonists based on the structure of the natural product, willardiine, we show that the charged state of the ligand determines the enthalpic contribution to binding. Willardiines have uracil rings with pKa values ranging from 5.5 to 10. The binding of the charged form is largely driven by enthalpy, while that of the uncharged form is largely driven by entropy. This is due at least in part to changes in the hydrogen bonding network within the binding site involving one water molecule. This work illustrates the importance of charge to the thermodynamics of binding of agonists and antagonists to AMPA receptors and provides clues for further drug discovery.
PDB ID: 4Q30Download
MMDB ID: 120529
PDB Deposition Date: 2014/4/10
Updated in MMDB: 2017/07
Experimental Method:
x-ray diffraction
Resolution: 2.03  Å
Source Organism:
Similar Structures:
Biological Unit for 4Q30: dimeric; determined by author and by software (PISA)
Molecular Components in 4Q30
Label Count Molecule
Proteins (2 molecules)
2
Glutamate Receptor 2 Chimeric Protein(Gene symbol: Gria2)
Molecule annotation
Chemicals (6 molecules)
1
2
2
4
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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