7k1a
From Proteopedia
TtgR quadruple mutant (C137I I141W M167L F168Y)
Structural highlights
FunctionTTGR_PSEPT Represses expression from the ttgABC operon promoter and its own expression. Binds to a promoter region between the divergently transcribed ttgR and ttgABC genes/operons; in the presence of chloramphenicol or tetracycline this binding no longer occurs and ttgR and ttgABC are derepressed. This suggests that TtgR binds these antibiotics.[1] Publication Abstract from PubMedEpistasis is a major determinant in the emergence of novel protein function. In allosteric proteins, direct interactions between inducer-binding mutations propagate through the allosteric network, manifesting as epistasis at the level of biological function. Elucidating this relationship between local interactions and their global effects is essential to understanding evolution of allosteric proteins. We integrate computational design, structural and biophysical analysis to characterize the emergence of novel inducer specificity in an allosteric transcription factor. Adaptive landscapes of different inducers of the designed mutant show that a few strong epistatic interactions constrain the number of viable sequence pathways, revealing ridges in the fitness landscape leading to new specificity. The structure of the designed mutant shows that a striking change in inducer orientation still retains allosteric function. Comparing biophysical and functional properties suggests a nonlinear relationship between inducer binding affinity and allostery. Our results highlight the functional and evolutionary complexity of allosteric proteins. Epistasis shapes the fitness landscape of an allosteric specificity switch.,Nishikawa KK, Hoppe N, Smith R, Bingman C, Raman S Nat Commun. 2021 Sep 21;12(1):5562. doi: 10.1038/s41467-021-25826-7. PMID:34548494[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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