Asymmetric dynamic coupling promotes alternative evolutionary pathways in an enzyme dimer.
| Autor: | Ambrus V; MTA-DE Laboratory of Protein Dynamics, Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary., Hoffka G; MTA-DE Laboratory of Protein Dynamics, Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary., Fuxreiter M; MTA-DE Laboratory of Protein Dynamics, Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary. monika.fuxreiter@unipd.it.; Department of Biomedical Sciences, University of Padova, Padua, Italy. monika.fuxreiter@unipd.it. |
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| Jazyk: | angličtina |
| Zdroj: | Scientific reports [Sci Rep] 2020 Nov 02; Vol. 10 (1), pp. 18866. Date of Electronic Publication: 2020 Nov 02. |
| DOI: | 10.1038/s41598-020-75772-5 |
| Abstrakt: | The importance of dynamic factors in enzyme evolution is gaining recognition. Here we study how the evolution of a new enzymatic activity exploits conformational tinkering and demonstrate that conversion of a dimeric phosphotriesterase to an arylesterase in Pseudomonas diminuta is accompanied by structural divergence between the two subunits. Deviations in loop conformations increase with promiscuity, leading to functionally distinct states, while they decrease during specialisation for the new function. We show that opposite loop movements in the two subunits are due to a dynamic coupling with the dimer interface, the importance of which is also corroborated by the co-evolution of the loop and interface residues. These results illuminate how protein dynamics promotes conformational heterogeneity in a dimeric enzyme, leading to alternative evolutionary pathways for the emergence of a new function. |
| Databáze: | MEDLINE |
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