Summary
Proteins can be engineered with new/different substrates by targeting the productive conformation using design strategies. In the example by (1), an aminotransferase is mutated to favor a conformation that allows transamination of phenylalanine. (2) describe how a mutation that stabilized a different active state of alpha-esterase from the crystallized conformation, leading to novel catalytic activity.
Details
The quote from (2): “Minor, but catalytically productive, substates thus appear to be responsible for the novel catalytic activity despite their low prevalence in the time-averaged enzyme population.”
See also
- Dynamics and specificity are inversely related
- Conformational sampling can smoothen fitness landscapes
- Protein dynamics
1.
St-Jacques AD, Rodriguez JM, Eason MG, Foster SM, Khan ST, Damry AM, et al. Computational remodeling of an enzyme conformational landscape for altered substrate selectivity. Nature Communications. 2023;14(1). Available from: https://doi.org/10.1038/s41467-023-41762-0
2.
Damry AM, Jackson CJ. The evolution and engineering of enzyme activity through tuning conformational landscapes. Protein Engineering, Design and Selection. 2021;34. Available from: https://doi.org/10.1093/protein/gzab009