Second coordination sphere regulates nanozyme inhibition to assist early drug discovery.

ABSTRACT: Early drug discovery is a time- and cost-consuming task requiring enzymes. Although nanozymes with metal sites akin to metallocofactors display similar activities, the lack of proximal amino acids hinders them from more adequately mimicking enzymes for drug discovery purposes. Hence, the rational design of the nanozyme second coordination sphere is desirable yet remains challenging. Herein, we report a nanozyme featuring atomically dispersed Cu-N₄ sites with proximal hydroxyl groups (CuNC-OH). Experimental and theoretical results reveal that Cu-N₄ site and hydroxyl respectively behave as cofactor and amino acid of the enzymatic pocket to interact with adsorbates, regulating nanozyme activity and inhibition. This mechanism involving dual sites is similar to that of thy

SUBMITTER: Wu Y 

PROVIDER: S-EPMC11961690 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature