The 'evolvability' of promiscuous protein functions

By A. Aharoni, L. Gaidukov, O. Khersonsky, Stephen McQ Gould, C. Roodveldt, Dan S. Tawfik. Nature Genetics, 2005

816 citations recorded by the source corpus.

Subfields: Biochemistry, Molecular Biology, Pharmacology

View Paper: https://www.semanticscholar.org/paper/2ccd773bea367373dd2cec704880d8b45ae2b3c0

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Citations in the corpus

A de novo protein binding pair by computational design and directed evolution (2011, background): “The Orientational Specificity of Protein Complexes In vitro evolved proteins are frequently found to be promiscuous, exhibiting a wide range of crossreactivity (Aharoni et al., 2005; Bridgham et al., 2006; Collins et al., 2006; James and Tawfik, 2003; Khersonsky et al., 2006).”
How Protein Stability and New Functions Trade Off (2008, background): “mutations to locate to random coils is also in accordance with the notion that the routes leading to new functions do not usually involve modification of either the enzyme's scaffold or key catalytic residues, but rather involve multiple, and often subtle, changes in loops that comprise the substrat”
Robustness, evolvability, and neutrality (2005, result): “Similar results hold for the other two enzymes [54].”
Evolving new protein-protein interaction specificity through promiscuous intermediates (2015, neutral): “Mutations that render proteins more promiscuous, with respect to catalytic activities or binding partners, has been noted anecdotally (Aharoni et al., 2005; Bloom and Arnold, 2009), but the prevalence of such states and, importantly, their accessibility from more specific, wild-type states has…”
Robustness and evolvability: a paradox resolved (2008, methodology): “Multiple definitions of robustness and evolvability are in use (Houle 1992; Kirschner & Gerhart 1998; Bedau & Packard 2003; Hansen 2003; Masel & Bergman 2003; Michod et al. 2003; Nijhoutet al. 2003; Earl & Deem 2004; Aharoni et al. 2005; Wagner 2005; Sniegowski & Murphy 2006).”
Probing the Mutational Interplay between Primary and Promiscuous Protein Functions: A Computational-Experimental Approach (2012, background): “Furthermore, as briefly elaborated below, promiscuity likely plays an essential role in the development of new functions through divergent evolution [3,5,8,16–20].”
The evolution of gene duplications: classifying and distinguishing between models (2010, background): “This requires that some gene copies in the population should pre-adapt to perform new functions while still performing the original function of the gen”
Enzyme promiscuity: a mechanistic and evolutionary perspective. (2010, methodology): “…weak trade-off trend was ﬁrst described in three different enzymes subjected to a selection for an increase in six different promiscuous activities (138), yet it was also observed in On , mutations increased the promis-cuous activity under selection by 10–10 6 -fold, whereas the original activity…”