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Since D100A is located in the binding pocket of the 5-HT4 recepthis this mutation in Rs1 may have changed the configuration of the binding pocket, making the receptor more susceptible to Gq activation by zacopride and RS23597.
The conserved intron insertion site, G307, seemed to be an especially important hinge region by which the working angle could be used to adapt to the global configuration of the binding surface.
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This is illustrated in Figure 19, where both the configurations of the binding sites and a sketch of the potential energy landscape are shown.
The configuration of this binding site is unexpected.
These sites had previously been implicated in the configuration of the AMP binding site.
Ambitiously, we firstly proposed a model in which the hydrophobic interaction of W60 with other two aromatic amino acids (F74 and W75) is critical for the maintenance of configuration of the DNA binding domain of FadR protein at N-terminus (Fig. 5).
This helical configuration of the metal binding motif leads to the presentation of the invariant acidic residues in the consensus sequence (D491, E497 and E502) on the same side of the helix towards the surface of the protein.
The overall configuration of the substrate binding site (GUA1) and the associated radical intermediate on Tyr71 (see Figure 2) is thus reminiscent of the situation in BpKatG (see Figure 3).
Some of these mutations alter specifically the configuration of the ATP-binding kinase pocket (V654A and T670I), inhibiting imatinib binding.
These structures show the same overall configuration of the Na+-binding sites (Fig. 2).
10.7554/eLife.03145.022 Figure 7. Configuration of the proton-binding site in asymmetric crystal structures of four AcrB variants inactive in drug efflux, compared to the wildtype protein.
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