Metal-responsive regulation of enzyme catalysis using genetically encoded chemical switches.

ABSTRACT: Dynamic control over protein function is a central challenge in synthetic biology. To address this challenge, we describe the development of an integrated computational and experimental workflow to incorporate a metal-responsive chemical switch into proteins. Pairs of bipyridinylalanine (BpyAla) residues are genetically encoded into two structurally distinct enzymes, a serine protease and firefly luciferase, so that metal coordination biases the conformations of these enzymes, leading to reversible control of activity. Computational analysis and molecular dynamics simulations are used to rationally guide BpyAla placement, significantly reducing experimental workload, and cell-free protein synthesis coupled with high-throughput experimentation enable rapid prototyping of variants. Ultimatel

SUBMITTER: Zubi YS 

PROVIDER: S-EPMC8987029 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature