An enzyme switch
A phosphatase from bacteria contains a structural element that acts as a switch to control the enzyme’s activity.
To regulate the activity of proteins, cells often modify them by adding or removing chemical groups called phosphates. Therefore, the enzymes that add or remove these phosphate groups must be tightly regulated so that they are active at the right time and place. Enzymes known as phosphatases remove phosphate groups from proteins and the PP2Cs are one such family of enzymes that are found in bacteria, plants and animals. Despite their broad importance, it was not clear how cells control the PP2Cs.
One way to understand how an enzyme is controlled is to compare the three-dimensional structures of the enzyme when it is active and when it is inactive. Niels Bradshaw and colleagues used a PP2C enzyme from bacteria as a model to understand how cells regulate other PP2Cs.
The experiments reveal that the bacterial enzyme has a structural element that acts as a switch to control its activity. The phosphatase needs to bind metal ions to be active, and movement of the switch promotes binding of the metal ions to activate the phosphatase. The switch is also found in other members of the PP2C family. Furthermore, members of a seemingly unrelated family of enzymes called the proteasomal proteases, which degrade proteins, also have a similar architecture and are controlled by a similar switch. Thus, the phosphatase and protease families may have a common evolutionary history.
Multiple members of the PP2C family are involved in cancer and other diseases. The discovery of a regulatory switch provides new opportunities to use drugs to control phosphatase activity in patients. Many cancer drugs that are currently in use or are under development target enzymes that add phosphate groups to proteins, but efforts to target the phosphatases have largely been unsuccessful. Bradshaw and colleagues’ findings may enable the development of new drugs that target protein phosphatases.
To find out more
Read the eLife research paper on which this eLife digest is based: “A widespread family of serine/threonine protein phosphatases shares a common regulatory switch with proteasomal proteases” (May 20, 2017).
