Allosteric ligands

In general, the kinetics of most allosteric modulators have been shown to be faster than the kinetics of binding of the tracer ligand. This is an initial assumption for this experimental approach. Under these circumstances, the rate of dissociation of the tracer ligand (pA t) n the presence of the allosteric ligand is given by [11, 12]... 

Jakubic, J., and El-Fakahany, E. E. (1997). Positive coopera -tivity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors. Mot. Pharmacol. 52 172-177. 

Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors. Mol. Pharmacol. 52 172—179. 

Comparison of proper ties of ortliosteric and allosteric ligands. 

Effects of allosteric ligands on response changing efficacy (7.7.2)... 

Effects of Allosteric Ligands on Response Changing Efficacy... 

Ehlert, F. J. (1988). Estimation of the affinities of allosteric ligands using radioligand binding and pharmacological null methods. Mol. Pharmacol. 33 187-194. 

Protein phosphorylation-dephosphorylation is a highly versatile and selective process. Not all proteins are subject to phosphorylation, and of the many hydroxyl groups on a protein s surface, only one or a small subset are targeted. While the most common enzyme function affected is the protein s catalytic efficiency, phosphorylation can also alter the affinity for substrates, location within the cell, or responsiveness to regulation by allosteric ligands. Phosphorylation can increase an enzyme s catalytic efficiency, converting it to its active form in one protein, while phosphorylation of another converts it into an intrinsically inefficient, or inactive, form (Table 9—1). 

Many proteins can be phosphorylated at multiple sites or are subject to regulation both by phosphorylation-dephosphorylation and by the binding of allosteric ligands. Phosphorylation-dephosphorylation at any one site can be catalyzed by multiple protein kinases or protein phosphatases. Many protein kinases and most protein phosphatases act on more than one protein and are themselves interconverted between active and inactive forms by the binding of second messengers or by covalent modification by phosphorylation-dephosphorylation. 

Schuller, D. J., Grant, G. A., and Banaszak, L.J. (1995). The allosteric ligand site in the Vmax-type cooperative enzyme phosphoglycerate dehydrogenase. Nat. Struct. Biol. 2, 69-76. 

Fig. 3.17 (A) ALIS-MS results from quenching an equilibrated mixture of 2.0 iM M2 receptor plus 1.5 pM NMS by 200 pM of the isosteric ligand NMS-D3, in the presence and absence of the known allosteric ligand W-84 at 50 pM concentration. Binding by the allosteric ligand W-84 decreases the off-rate of NMS. (B) Compound structures.

Ehlert, F.L. Estimation of the affinities of allosteric ligands using... 

Nichol and Winzor described the binding equations that apply to such hgand-induced changes in receptor oligomerization. They also presented the following equation to describe the joint operation of allosteric ligand binding cooperativity and receptor self-association. 

GPR88, GABABL Glutamate GABA-B allosteric ligands... 

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