Forschung

Systemic approach:

1. What are the absolute stoichiometries of lysine acetylation and other lysine acylations on a whole proteome scale (Fig. 3A)?
2. How is lysine acetylation regulated by KATs?
3. How are KAT enzymes of pathogens such as Yersina, Vibrio, Legionella, Salmonella species and viruses such as the Borna Disease Virus (BDV) catalysing the transfer of acetyl-groups what are their substrates in the host cell?

Targeted approach:

1. How are different lysine acylations, such as succinylation, palmitoylation, acetylation, butyrylation etc., functionally distinct to regulate protein-function? Do they occur simultaneously or mutually exclusive on lysines (Fig. 3B)? 
2. Which sites are regulated by lysine-deacetylases (KDACs) and lysine-acetyltransferases (KATs) as an evidence for its biological significance (Fig. 3C)?
3. What determines the specificity of lysine-deacetylases for substrate proteins (Fig. 3C)?
4. How are sirtuins endogenously regulated in mammalian cells?
5. How does the incorporation of acetyl-lysine analogues into peptides/proteins derived from natural KDAC-substrates behave as mechanistic KDAC inhibitors? Are they potential therapeutics (Fig. 3D)?