Mechanistic conformational and substrate selectivity profiles emerging in the evolution of enzymes via parallel trajectories.
Autor: | Karamitros CS; Department of Chemical Engineering, University of Texas at Austin (UT Austin), Austin, TX, USA.; Research and Clinical Development, Nestlé Health Science, Lausanne, 1000, Switzerland., Murray K; Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, TX, USA.; Trajan Scientific America's, Inc. Boston, Massachusetts, MA, USA., Kumada Y; Department of Molecular Chemistry and Engineering, Kyoto Institute of Technology, Kyoto, Japan., Johnson KA; Department of Molecular Biosciences, University of Texas at Austin (UT Austin), Austin, TX, USA., D'Arcy S; Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, TX, USA., Georgiou G; Department of Chemical Engineering, University of Texas at Austin (UT Austin), Austin, TX, USA. gg@che.utexas.edu.; Department of Molecular Biosciences, University of Texas at Austin (UT Austin), Austin, TX, USA. gg@che.utexas.edu.; Department of Biomedical Engineering, University of Texas at Austin (UT Austin), Austin, TX, USA. gg@che.utexas.edu.; Institute for Cellular and Molecular Biology, The University of Texas at Austin (UT Austin), Austin, TX, USA. gg@che.utexas.edu. |
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Jazyk: | angličtina |
Zdroj: | Nature communications [Nat Commun] 2024 Aug 16; Vol. 15 (1), pp. 7068. Date of Electronic Publication: 2024 Aug 16. |
DOI: | 10.1038/s41467-024-51133-y |
Abstrakt: | Laboratory evolution studies have demonstrated that parallel evolutionary trajectories can lead to genetically distinct enzymes with high activity towards a non-preferred substrate. However, it is unknown whether such enzymes have convergent conformational dynamics and mechanistic features. To address this question, we use as a model the wild-type Homo sapiens kynureninase (HsKYNase), which is of great interest for cancer immunotherapy. Earlier, we isolated HsKYNase_66 through an unusual evolutionary trajectory, having a 410-fold increase in the k (© 2024. The Author(s).) |
Databáze: | MEDLINE |
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