Molecular mechanism and inhibition of bacterial and human zinc proteases

It is an urgent need to develop new effective strategies against bacterial infections with a low risk for resistance development. Most enzyme of the M4 family of zinc metalloproteinases are virulence factors secreted from gram-positive or gram-negative bacteria. These enzymes degrade extracellular proteins and peptides that the bacteria uses for nutrition prior to sporulation. The family includes enzymes from pathogens such as Legionella, Listeeria, Clostridium, Staphylococcus, Pseudomonas and Vibrio. Inhibitors of M4 enzymes may weaken the pathogen and be a putative strategy in the fight against bacterial infections.  In order to have therapeutic potentials, bacterial M4 enzyme inhibitors should not interfere with the substrate degradation of endogenous zinc metalloproteinases of the infected host, like the matrix metalloproteinases (MMPs). We are using a combination of enzyme inhibition and kinetics studies and molecular modelling to study molecular mechanisms of the inhibition of M4 enzymes and different human zinc metalloproteinases. The project is a collaboration with prof. Jan-Olof Winberg, Department of Medical Biology and international partners.    

 

Bachelor, master and PhD –projects

Depending on financing and supervising capacity bachelor-, master- and PhD-project can be offered connected to the project.


Ansvarlig for prosjektet: Zvonko Mitrovic

Principal investigator:

Ingebrigt Sylte

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