Sebastian Mathea

This paper elucidates the structural mechanisms by which LRRK2 is activated and autoinhibited, showing how mutations affect these processes and suggesting therapeutic strategies.

This paper determines the crystal structures of DFCP1's ATPase domain with ADP and ATP analogues, revealing structural elements that regulate ATP hydrolysis and omegasome dynamics.

This study uses proximity labeling and phosphoproteomics to analyze LRRK1 and LRRK2 interactomes and phosphorylation sites, identifying novel substrates and the impact of inhibitors.

The paper identifies novel kinase:Rab pairs and characterizes substrate recognition determinants for Rab phosphorylation by kinases like LRRK2.

The paper develops pyrazolopyrimidine-based macrocyclic kinase inhibitors targeting AAK1, showing selectivity over related NAK family members and antiviral activity against RNA viruses.

This study develops a covalent LIMK1 inhibitor that selectively targets a unique cysteine, enabling isoform-specific studies of LIMK1 function.

Hybrid type-II inhibitors RN277 and RN341 target inactive LRRK2 with far fewer kinase off-targets than Rebastinib, preserve S935 phosphorylation, and rescue kinesin motility in vitro.

The paper repurposes a benzoxazepinone scaffold originally designed for RIPK1 inhibition to develop a novel type-III LIMK1/2 inhibitor with high selectivity.

This study identifies TOM20, TOM70, TOM40, and associated subunits as critical for PINK1 activation in a reconstituted yeast system, providing insights for PINK1 activator development.

The paper describes efforts to crystallize the Parkinson’s disease protein LRRK2 under microgravity conditions to improve diffraction quality for structure determination.