These two motifs cause a substrate to act as a coupled system in which a unidirectional cycle generates single-molecule oscillators, whereas sequestration synchronizes the population by limiting the available enzyme under conditions in which substrate is in excess.
However, the Gibbs motif sampler has a serious drawback in that inherent presence of a great many different motifs causes a complex energy landscape of the posterior distribution.
It is still an improvement on HMM-based approaches where modeling even partial overlap of motifs causes a combinatorial increase in the state space.
Mutations in the conserved HG motifs cause a renal salt-wasting syndrome called pseudohypoaldosteronism type 1 (PHA-1) [ 85], and mutations in the conserved PPPXY motif in β- and γ-ENaC subunits are associated with Liddle's syndrome, a form of monogenic hypertension [ 86, 87].
Mutation of the ABBA motif caused a reproducible 1.5- to 2-fold decrease in maximal catalytic activity (Fig. 1).
Careful redefinition of a specific GlnR-binding and a specific TnrA-binding motif caused a slight but clear separation in the predicted regulons.
As observed in comparison of the F10, F08, and F23 constructs, the presence of the CDE1 motif plus either the CGC motif or the CCG motif caused a high level of constitutive expression of the target gene.
Moreover, mutation of the Gata motif caused a relatively mild reduction compared to mutation of the Ets motifs, suggesting that Gata factors are not critically required to activate the Scl+19.
Deletion of the UIM motif caused a marked reduction in NEDD8-binding and had no effect on ubiquitin-binding, while UBA-deletion abolished ubiquitin-binding and caused some reduction in NEDD8-binding as well.
Moreover, the two closely apposed mutations, 681 689del and Y699C, which are located immediately adjacent to the hook motif, caused a more severe reduction in interaction with FRMD7 than W890R.
