Binding site model, noncompetitive

Figure 8. A Model of the Binding Site for Noncompetitive GABA Receptor Antagonists. The Orientation of Fipronil Remains to Be Determined.

There may be a possible receptor for REE on the plant cell surface (most likely NADPH oxidase), and binding of REE to the receptor possibly leads to an immediate OXB. The noncompetitive mode of interaction between La and Zn implies that Zn may bind to both the La-bound form and La-ffee form of the putative receptor, thus expressed as R -t I RI, RL -i- I <-> RLI where R is the receptor, L is a ligand (La), I is an inhibitor (Zn). RI, RL and RLI are receptor complexes with other factors. This result suggests that the site of Zn binding on the target molecule is different from the REE binding site. In the future, this model must be examined in the purified and reconstituted Oa -generating systems. 

Malherbe P, Kratochwil N, Knoflach F et al (2003) Mutational analysis and molecular modeling of the allosteric binding site of a novel, selective, noncompetitive antagonist of the metabotropic glutamate 1 receptor. J Biol Chem 278 8340-8347... 

Casida JE, Tomozawa M (2008) Insecticide Interaction with y-Aminobutyric Acid and Nicotinic Receptors Predictive Aspects of Stractural Models. J Pestic Sci 33 4 Chen LG, Durkin KA, Casida JE (2006) Stractural Model for y-Aminobutyric Acid Receptor Noncompetitive Antagonist Binding Widely Diverse Structures Fit the Same Site. Proc Nat Acad Sci USA 103 5185... 

In the simplest monosubstrate case, a noncompetitive inhibitor would have no effect on substrate binding and vice versa. The inhibitor and the substrate bind reversibly, randomly, and independently at different sites. The substrate binds to E and El, and the inhibitor binds to E and EA however, the resulting EAI complex is inactive. The binding of one ligand has no effect on the dissociation constant of the other therefore, both binding reactions E + A EA and El + A EAI have the same dissociation constant. The kinetic model for this type of inhibition would be... 

In the noncompetitive inhibitor model, the binding of X to F is independent of the binding of Y to F v(x) is independent of Kyy. This can result from an independence of the two sites. Y regulates, controls, or shuts down an effect or activity of F in some way that does not involve the binding of X to P. 

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