The crystal structure of an analogue (44) was solved and provided rationalization of the SAR of this series, which binds in a distinct manner in the palm domain of NS5B, consistent with biochemical analysis using enzyme mutant variants.
The structural data suggest that the ETGE and DLG motifs each bind to Keap1 in a distinct manner, and that the "rapid association dissociation" nature of the DLG interaction means that it is sometimes bound to Keap1 and sometimes unbound (Fukutomi et al., 2014).
Whereas, the alanine substitution of Val at position 4 reduced the binding affinity to the maximum extent and bound HLA-DR in a distinct manner from TP5, projecting out the cleft (Fig. 6E).
Interestingly, pyrabactin binds to PYL3 in a distinct nonproductive mode with gate closure, which sheds light on the design of agonists and antagonists for abscisic acid receptors.
The existence of this conformation is supported by structural studies which have shown that the DLG motif binds to Keap1 in a distinct mode from the ETGE motif, with "fast on fast off" kinetics (Fukutomi et al., 2014).
SRF can also bind to a distinct promoter element found in many genes that encode actin cytoskeleton associated proteins [19].
For an SM to exhibit selectivity for its cognate SNARE-Sec17 complex without direct SM-SNARE contacts, Sec17 would need to bind each SNARE complex in a distinct conformation, and these conformational differences would then need to be transmitted to, and recognized by, the SM.
When introducing the excluded volumes of the new D1 pharmacophore model we discovered that the D1 agonists may bind in two distinct binding modes involving two different receptor binding site conformations.
Since IFNs λ bind to a distinct membrane receptor, they would not be detected in the bioassay used here.
Membrane proteins are unique, in that they can function properly only when they are bound to cellular membranes in a distinct manner.
