We are a research group at the University of Ljubljana, Faculty of Chemistry and Chemical Technology.
We investigate the molecular basis of life with focus on the structure, function and evolution of proteins and their regulation by small molecules and macromolecules using a combination of experimental and computational methods.
25-07-2021 – Tjaša’s paper “Synthesis and kinetic characterization of hyperbolic inhibitors of human cathepsins K and S based on a succinimide scaffold” describing the first hyperbolic inhibitors of cathepsin S was published in Bioorganic Chemistry. The online version is available here.
Most enzymes prefer to assemble into oligomers rather than function as stand-alone monomers. One of the profound advantages of oligomeric structure is cooperativity between subunits. Despite the advantages, not all enzymes are cooperative oligomers. Our aim is to investigate whether natural monomeric enzymes would also benefit from oligomerization and cooperativity.
ALLOSTERY IN PAPAIN-LIKE PEPTIDASES
Allosteric regulation is an important mechanism in proteins where binding of ligand at one site results in conformational and functional changes at a second, spatially distant site. Allosteric targeting of proteins is gaining increasing recognition as a strategy in drug design. We are investigating allostery in papain-like cysteine peptidases with the aims of understanding how allosteric communication is transmitted in these proteins and discovering novel allosteric effectors of these enzymes.
OLIGOMERIZATION OF DPPI
Dipeptidyl peptidase I (DPPI) is unique among human papain-like peptidases in that it is a tetramer, not a monomer. Tetramerization is enabled by the additional exclusion domain that is unique to DPPI. We are investigating the evolutionary history and diversity of oligomeric states of DPPI.
Identification and characterization of novel protein/small molecule interactions with focus on the discovery of novel antibiotics and anti-cancer drugs.