The Zelikin group publishes in Nature Communications
Nature knows how to activate and deactivate enzymes on demand, without wasteful protein synthesis and degradation. Surprisingly, methods to do so using tools of chemistry are few. PhD candidate Mireia Casanovas Montasell, Prof. Alexander N. Zelikin and colleagues address this challenge in their new publication, published in Nature Communications.
Mechanisms of reversible protein deactivation are foundational in life. For example, these mechanisms are used by cells in signaling cascades, whereby multiple enzymes undergo controlled activity switch on/off events, which ultimately connects external signals to internal cellular responses. The Zelikin group focused on the protein cysteinome – proteins with cysteine amino acid – and designed chemical zymogens such that enzyme activity can be switched on demand using tools of chemistry. The key to the proposed designs in the reversible character of disulfide linkages.
Three classes of zymogens were designed and applied to three different enzymes, thus presenting a robust, reliable chemical platform for zymogen design. These are now being developed further, towards establishing signaling in artificial cells.
|ITEM||CONTENT AND PURPOSE|
|Type of study/ |
|Journal article (peer reviewed)|
|External collaborators||No external collaborators|
|External funding||DFF FNU (Grant No 0135-00162B) |
Novo Nordisk Foundation NERD grant (Grant No NNF20OC0062131)
Carlsberg Foundation (Grant No CF19-0275)
Lundbeck Foundation (Grant No R287-2018-1117)
|Conflict of interest||No conflicts of interest|
|Link to the scientific article||https://www.nature.com/articles/s41467-022-32609-1|
|Contact information||Prof. Alexander Zelikin |
Department of Chemistry and iNANO, Aarhus University