Unnatural enzyme activation by a metal-responsive regulatory protein.

ABSTRACT: As a result of calcium ion binding, the calcium-dependent regulatory protein calmodulin (CaM) undergoes a conformational change, enabling it to bind to and activate a variety of enzymes. However, the detoxification enzyme glutathione S-transferase (GST) is notably not among the enzymes activated by CaM. In this study, we demonstrate the feasibility of establishing, in vitro, an artificial regulatory link between CaM and GST using bifunctional chemical transducer (CT) molecules possessing binders for CaM and GST. We show that the CTs convert the constitutively active GST into a triggerable enzyme whose activity is unnaturally regulated by the CaM conformational state and consequently, by the level of calcium ions. The ability to reconfigure the regulatory function of CaM demon

SUBMITTER: Halfin O 

PROVIDER: S-EPMC11322901 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature