Liskova_2015_ChemCatChem_7_648

Reference

Title : Balancing the stability-activity trade-off by fine-tuning dehalogenase access tunnels - Liskova_2015_ChemCatChem_7_648
Author(s) : Liskova V , Bednar D , Prudnikova T , Rezacova P , Koudelakova T , Sebestova E , Kuta-Smatanova I , Brezovsky J , Chaloupkova R , Damborsky J
Ref : ChemCatChem , 7 :648 , 2015
Abstract :

A variant of the haloalkane dehalogenase DhaA with greatly enhanced stability and tolerance of organic solvents but reduced activity was created by mutating four residues in the access tunnel. To create a stabilized enzyme with superior catalytic activity, two of the four originally modified residues were randomized. The resulting mutant F176G exhibited 10- and 32-times enhanced activity towards 1,2-dibromoethane in buffer and 40% (v/v) DMSO, respectively, while retaining high stability. Structural and molecular dynamics analyses showed that the new variant exhibited superior activity because the F176G mutation increased the radius of the tunnel's mouth and the mobility of alpha-helices lining the tunnel. The new variant's tunnel was open in 48 % of trajectories, compared to 58 % for the wild-type, but only 0.02 % for the original four-point variant. Delicate balance between activity and stability of enzymes can be manipulated by fine-tuning the diameter and dynamics of their access tunnels.

PubMedSearch : Liskova_2015_ChemCatChem_7_648
PubMedID:
Gene_locus related to this paper: rhoso-halo1

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Citations formats

Liskova V, Bednar D, Prudnikova T, Rezacova P, Koudelakova T, Sebestova E, Kuta-Smatanova I, Brezovsky J, Chaloupkova R, Damborsky J (2015)
Balancing the stability-activity trade-off by fine-tuning dehalogenase access tunnels
ChemCatChem 7 :648

Liskova V, Bednar D, Prudnikova T, Rezacova P, Koudelakova T, Sebestova E, Kuta-Smatanova I, Brezovsky J, Chaloupkova R, Damborsky J (2015)
ChemCatChem 7 :648