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Enzyme promiscuity: a mechanistic and evolutionary perspective.
The hypothesis that promiscuous enzymatic activities serve as evolutionary starting points and highlight the unique evolutionary features ofpromiscuous enzyme functions are addressed. Expand
Kemp elimination catalysts by computational enzyme design
The computational design of eight enzymes that use two different catalytic motifs to catalyse the Kemp elimination—a model reaction for proton transfer from carbon—with measured rate enhancements of up to 105 and multiple turnovers are described. Expand
Man-made cell-like compartments for molecular evolution
It is demonstrated the linkage of genotype to phenotype in man-made compartments using a model system and a selection for target-specific DNA methylation was based on the resistance of the product (methylated DNA) to restriction digestion. Expand
Antibody Multispecificity Mediated by Conformational Diversity
A single antibody was shown to adopt different binding-site conformations and thereby bind unrelated antigens, which can increase the effective size of the antibody repertoire but may also lead to autoimmunity and allergy. Expand
Stability effects of mutations and protein evolvability.
Way of predicting and analyzing stability effects of mutations, and mechanisms that buffer or compensate for these destabilizing effects and thereby promote protein evolvabilty, in nature and in the laboratory are described. Expand
Structure-reactivity studies of serum paraoxonase PON1 suggest that its native activity is lactonase.
PON1 is the best-studied member of a family of enzymes called serum paraoxonases, or PONs, identified in mammals (including humans) and other vertebrates as well as in invertebrates. PONs exhibit aExpand
Protein Dynamism and Evolvability
This work considers an alternative, “avant-garde view” in which proteins are conformationally dynamic and exhibit functional promiscuity, and surmise that these properties are the foundation stones of protein evolvability. Expand
The moderately efficient enzyme: evolutionary and physicochemical trends shaping enzyme parameters.
It appears that both evolutionary selection pressures and physicochemical constraints shape the kinetic parameters of enzymes, and it seems likely that the catalytic efficiency of some enzymes toward their natural substrates could be increased in many cases by natural or laboratory evolution. Expand
The stability effects of protein mutations appear to be universally distributed.
This bi-Gaussian model provides an analytical description of the predicted distributions of mutational stability effects and comprises a novel tool for analyzing proteins and protein models, for simulating the effect of mutations under evolutionary processes, and a quantitative description ofmutational robustness. Expand
The latent promiscuity of newly identified microbial lactonases is linked to a recently diverged phosphotriesterase.
This work attempted to trace the origins of a bacterial phosphotriesterase (PTE), an enzyme thought to have evolved for the purpose of degradation of a synthetic insecticide introduced in the 20th century, and identified three genes that define a new group of microbial lactonase dubbed PTE-like lactonases (PLLs), which proficiently hydrolyze various lactones, and in particular quorum-sensing N-acyl homoserine lactones. Expand