My main field of research has been the creation and application of chemical tools to study ubiquitin and ubiquitin-like protein deconjugating enzymes. I started by developing a fluorescence polarization assay to assess ubiquitinated peptide selectivity of DUBs which turned out to be crucial in the elucidation of Ub linkage specificities of OTU DUBs (Cell 2013). I extended this technique to Ub-like proteins to assess bacterial effector proteases and the ISG15-specific protease USP18 (MolCell 2016 and FEBSJ 2014). This work laid the basis for the development of full-length diUb FRET probes with which the Ub linkage specificity of DUBs can be quantified (ChemBioChem 2016). These reagents proved to be key in the elucidation of the Lys11 specificity of Cezanne (Nature 2016).
I have also worked on Ub and Ub-like protease probes and I was heavily involved in the development of the selective Ub-propargylamide probe (JACS 2013). I also expanded this to the Ub-like field which has, among other things, resulted in the first crystal structure between full-length ISG15 and USP18 (NSMB 2017). Currently, I am developing small-molecule cell permeable DUB inhibitors and activity-based probes.
I completed my PhD (cum laude) in (bio-)organic chemistry at the Leiden Institute of Chemistry on the development of inhibitors and activity-based probes for matrix metalloproteases and active proteasomal subunits. In 2010 I joined the Ovaa group at the NKI as post-doc working on the design of novel tools to specifically target deubiquitinating enzymes. I moved to the LUMC in 2016 and became assistant professor in the Ovaa group. I am also currently heading the LUMC high-throughput screening facility.
Native chemical ligation at methionine bioisostere norleucine allows for N-terminal chemical protein ligation.
Xin BT, van Tol BDM, Ovaa H, Geurink PP.*
Org. Biomol. Chem. 2018, 16, 34, 6306-6315
Development of Diubiquitin-Based FRET Probes To Quantify Ubiquitin Linkage Specificity of Deubiquitinating Enzymes.
Geurink PP*, van Tol BD, van Dalen D, Brundel PJ, Mevissen TE, Pruneda JN, Elliott PR, van Tilburg GB, Komander D, Ovaa H.;
Chembiochem 2016, 17, 9, 816-820.
Structural basis of the specificity of USP18 toward ISG15.
Basters A, Geurink PP, Röcker A, Witting KF, Tadayon R, Hess S, Semrau MS, Storici P, Ovaa H, Knobeloch KP, Fritz G.;
Nat. Struct. Mol. Biol. 2017, 24, 3, 270-278.