Dr Sebastian Guettler

Dr Sebastian Guettler - Research Interests

We employ biochemical techniques, X-ray crystallography, electron microscopy (with Dr Edward Morris) and functional studies in mammalian cells to unravel the mechanisms underlying the cellular functions of ADP-ribosyltransferases (ARTs). We study the poly(ADP-ribose)polymerase Tankyrase and other ART family members with a particular interest in:

(1) understanding the regulation of ART enzymatic activities,

(2) identifying novel ART-substrate relationships and the substrate recognition mechanisms involved, and

(3) developing novel approaches for ART inhibition through an increased understanding of the enzymes’ mode of action.

Structural representation of a substrate binding module of Tankyrase bound to substrate

Using a structure-function approach, we aim to study the modes of action, substrate recognition and regulation of ADP-ribosyltransferases. The figure shows a structural representation of a substrate binding module of Tankyrase bound to substrate and crystals grown from this complex.

Relevant Publications

Guettler, S., Larose, J., Petsalaki, E., Gish, G., Scotter, A., Pawson, T., Rottapel, R., Sicheri, F. (2011). Structural basis and sequence rules for substrate recognition by Tankyrase explain the basis for cherubism disease. Cell 147:1340-54.