We are a research group at the University of Ljubljana, Faculty of Chemistry and Chemical Technology. Our research focuses on enzyme regulation, evolution, and engineering using a combination of experimental and computational methods.
Most enzymes prefer to assemble into oligomers rather than function as independent monomers. One of the profound advantages of oligomeric structure is cooperativity between subunits. Nevertheless, not all enzymes are cooperative oligomers. Our goal is to investigate whether naturally 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.