Projects
Structure-based design of HBV polymerase inhibitors KU Leuven
Cidofovir ((S)-HPMPC), a compound discovered by Antonin Holy, was developed in 1986 for treatment of cytomegalovirus (CMV) retinitis. This compound has a hydroxymethyl substituent engrafted on a phosphonomethoxyethyl (PME) backbone structure. Previously, analogues with a PME backbone as well as phosphonomethoxypropyl nucleoside (PMPA) series were described as active compounds against HIV and Hepatitis B (HBV). The drug activity could arise ...
Molecular mechanism of calcium signaling in muscle contraction Vrije Universiteit Brussel
Development of an affinity grid for cryo-electron microscopy enabling protein structure determination. University of Antwerp
High resolution structure determination of therapeutically relevant proteins as a means to validate an affinity grid for cryo-electron microscopy. University of Antwerp
Identification and characterization of clinically relevant cys-loop receptors. KU Leuven
Pentameric ligand-gated ion channels (pLGICs) are of high clinical relevance due to their central role in fast synaptic neurotransmission in both the central and peripheral nervous system. They are involved in the disease mechanism of numerous disorders including Alzheimer’s disease, myasthenia gravis, epilepsy and startle disease. Unraveling the 3-dimensional structures of pLGICs can provide insights in ligand recognition, channel gating, ...
Structural study and integrative modelling of the yeast Sin3/Rpd3 histone deacetylase complexes KU Leuven
Histone deacetylase (HDAC) enzymes are the main transcriptional repressors in eukaryotes. They do not work in isolation but function within multi-subunit complexes with different associating proteins. Among HDAC machineries, the Sin3 HDAC complex is involved in various cellular processes and diseases. However, the molecular assemblies of Sin3 HDAC complexes remain poorly understood with limited knowledge about how the assembly of the complex ...
Structure-based design of ribonucleoside triphosphate (rNTP) analogs targeting bacterial RNA polymerases KU Leuven
Structure-based design of ribonucleoside triphosphate (rNTP) analogs targeting bacterial RNA polymerases KU Leuven
The emergence of antibiotic resistance is among the leading public health concern worldwide. While the restricted use of antibiotic is adopted as a general practice to minimize the emergence of resistant bacteria, the discovery of new drugs is of urgent need. Inhibitors targeting bacterial RNA polymerase (RNAP) are used for treating several bacterial infections. Rifampicin is used to treat infections caused by mycobacteria tuberculosis and ...
Structural bases of γ-secretase processivity in Familial Alzheimer's Disease KU Leuven
Early onset familial Alzheimer’s disease (FAD) is a hereditary form of Alzheimer’s disease (AD) which is caused by mutations in Presenilin 1 (PSEN1), Presenilin 2 (PSEN2) or the Amyloid precursor protein (APP) genes. Aβ peptides are generated by PSEN carboxipeptidase activity of γ-secretase (GSEC) at the γ-sites, during these processes APP is cut in a sequential manner every three (and rarely four or five) amino acids at a time, generating ...