[Zoom Seminar] "Harnessing Conformational Dynamics to Engineer New Enzymes" by Prof. Lynn Kamerlin, Uppsala University
- Zoom link: https://oist.zoom.us/j/99559978434?pwd=cVJOK2R3QVVjbHBHTkZzUEFDaVVYZz09
- Meeting ID: 995 5997 8434
- Meeting Password: 012668
Speaker: Prof. Lynn Kamerlin, Uppsala University
Title: Harnessing Conformational Dynamics to Engineer New Enzymes
Understanding how new enzyme functions evolve, either on existing scaffolds, or completely de novo on previously non-catalytic scaffolds, is of great interest both from a fundamental biochemistry perspective, and from a biotechnological perspective. Several hypotheses have been put forward to rationalize enzyme evolution, one of which is that their conformational dynamics plays an important role in facilitating the emergence of new enzyme functions1-3. My team and I have invested substantial research effort into understanding enzyme multifunctionality in catalytically promiscuous enzymes4-8, as well as the structure-function-dynamics relationships shaping the evolution of new enzyme functions, in both natural and engineered active sites9-13. In this talk, I will discuss recent progress in this area, and illustrate how we have engineered conformational dynamics to generate a a de novo active site capable of catalysing a non-natural reaction,10 and then subsequently enhanced this activity using a simple computational approach, reaching catalytic efficiency comparable to that of naturally occurring enzymes.
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10. V. A. Risso, S. Martinez-Rodriguez, A. M. Candel, D. M. Krüger, D. Pantoja-Uceda, M. Ortega-Muñoz, F. Santoyo-Gonzalez, E. A. Gaucher, S. C. L. Kamerlin, M. Bruix, J. A. Gavira and J. M. Sanchez-Ruiz, Nat. Commun., 2017, 8, 16113.
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13. M. Kaltenbach, J. R. Burke, M. Dindo, A. Pabis, F. S. Munsberg, A. Rabin, S. C. L. Kamerlin, J. P. Noel and D. S. Tawfik, Nat. Chem. Biol., 2018, 14, 548-555.