Article
Evolutionary-scale enzymology enables exploration of a rugged catalytic landscape.
Science (New York, N.Y.) - 12 Jun 2025
Muir Duncan F, Asper Garrison P R, Notin Pascal, Posner Jacob A, Marks Debora S, Keiser Michael J, Pinney Margaux M
Abstract excerpt
Quantitatively mapping enzyme sequence-catalysis landscapes remains a critical challenge in understanding enzyme function, evolution, and design. In this study, we leveraged emerging microfluidic technology to measure catalytic constants-kcat and KM-for hundreds of diverse orthologs and mutants of adenylate kinase (ADK). We dissected this sequence-catalysis landscape's topology, navigability, and mechanistic...
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