Evolutionary-Scale Enzymology Enables Biochemical Constant Prediction Across a Multi-Peaked Catalytic Landscape.

ABSTRACT: Quantitatively mapping enzyme sequence-catalysis landscapes remains a critical challenge in understanding enzyme function, evolution, and design. Here, we expand an emerging microfluidic platform to measure catalytic constants-k _cat and K _M-for hundreds of diverse naturally occurring sequences and mutants of the model enzyme Adenylate Kinase (ADK). This enables us to dissect the sequence-catalysis landscape's topology, navigability, and mechanistic underpinnings, revealing distinct catalytic peaks organized by structural motifs. These results challenge long-standing hypotheses in enzyme adaptation, demonstrating that thermophilic enzymes are not slower than their mesophilic counterparts. Combining the rich representations of protein sequences provided by

SUBMITTER: Muir DF 

PROVIDER: S-EPMC11526920 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature