Changing the position of the macrocycle in a well-determined way is possible, by making the binding affinity of the less occupied station more favorable, or by destabilizing the interaction between the most occupied station and the macrocycle.
ATP counters the AMP effect not only by competitively binding to the γ-subunit, but also by destabilizing the interaction between the AID-αRIM and the γ-subunit independently of adenine nucleotide binding to CBS-3.
In the inactive state of EGFR, L861 packs up against hydrophobic residues in the C-helix [20], and this observation previously led to the suggestion that the L861Q mutation may activate EGFR by destabilizing the hydrophobic interactions in the inactive state [10], [46], [48].
Some regulators act by increasing (enhancers) or decreasing (repressors) the rates of transcription by stabilizing or destabilizing the interactions of the polymerase with the DNA or the auxiliary components, respectively.
The mechanistic consequences of the PIP2-mediated N-term/ICL4 association that emerge from this analysis are the disruption of a conserved IC network of ionic interactions, which triggers the inward-opening by destabilizing the IC network of ionic interactions, and the associated release of the Na+ ion from the Na2 site causes destabilization of the substrate DA in the primary S1 site.
While stabilizing the CBM-KD interaction and inducing formation of the C-interacting helix is associated with AMPK activation, destabilizing the interaction by mutating S108 in β1-containing AMPK complexes reduces AMPK activity.
In this work, the NMR results and the weaker affinity observed by ITC suggests that the VAMP truncations make SNAP-25 and also syntaxin more flexible and unstructured, thus destabilizing the interaction with complexin as well, resulting in lower FRET.
Third, class II mutations affecting intra-blade interactions of RHD indirectly impair its interaction with RID likely by destabilizing the predicted rigid structure of the RCC1-like propeller scaffold.
Designed mutation shows that switching interactions enhance the rate, perhaps by destabilizing the ground state immediately before the transition state and limiting nonproductive diffusion before and after the chemical transition state, thereby reducing the activation entropy.
In the scale-free molecular network, targeted disruption of limited numbers of critical components designated hubs, on which the biologically important molecular interactions concentrate, efficiently disturbs the whole cellular function by destabilizing the network [ 9].
