Single-Molecule DNA Tweezers Enable Programmable Control of Enzyme Activity via Arbitrary Molecular Cues.

ABSTRACT: Engineering allosteric control sites into enzymes typically requires extensive protein modification. Here, we introduce single-molecule DNA tweezers (SMDTs), which enable programmable, allosteric-like regulation of enzyme activity in response to user-defined chemical cues, without altering the enzyme itself. SMDTs consist of two aptamers connected by a tunable, stimuli-responsive DNA linker. By binding non-covalently to two distinct sites on an enzyme, the SMDT adopts a "pinched" conformation, reminiscent of mechanical tweezers, that inhibits enzymatic activity. Upon exposure to specific molecular triggers, the SMDT undergoes a conformational change that releases the inhibitory aptamer, restoring function. The degree of inhibition and reactivation efficiency can be finely tuned by adjustin

SUBMITTER: Godhulayyagari S 

PROVIDER: S-EPMC12624326 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature