Group of Proteases of Human Pathogens
Head: Jan Konvalinka

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Research projects

The research in our laboratory deals with the analysis of structure, activity and inhibition of medicinally relevant proteases and other enzymes as pharmaceutical targets. We are focused on the three major topics:

• structure - function analysis and inhibition of HIV protease developed under the selection pressure in HIV-positive patients treated with protease inhibitors
• expression, cellular localization, structure, function and inhibition of glutamate carboxypeptidase II, a neuropeptidase and cancer marker
• expression, characterization and structure of human serine racemase

The projects are different yet complementary and enable sharing of resources, instrumentation and expertise. These broadly based biological projects provide suitable topics for diploma- and PhD- thesis for the students of biochemistry and biology at the Charles University who represent the bulk of the lab manpower.

• HIV protease: structure, function, development of resistance and novel inhibitors
  
  
  • Cígler et al. (2005). From non-peptide towards non-carbon protease inhibitors: metallacarboranes as specific and potent inhibitors of HIV protease. Proc. Natl. Acad. Sci. USA 102, 15394-15399.
    
    
  • Prejdová et al. (2004). Determining and Overcoming Resistance to HIV Protease Inhibitors. Current Drug Targets -Infect. Disord. 4, 137-152.
    
    
  • Weber et al. (2002). Unusual binding mode of an HIV-1 protease inhibitor explains its potency against multi-drug-resistant virus strains. J. Mol. Biol. 324, 739-754.
    
    
  
  
• Glutamate carboxypeptidase II as an emerging pharmaceutical target
  
  
  • Bařinka et al. (2002). Substrate Specificity, Inhibition and Enzymological Analysis of Recombinant Human Glutamate Carboxypeptidase II. J. Neurochem. 80, 477-487.
    
    
  • Mesters et al. (2006). Structure of Glutamate Carboxypeptidase II, a Drug Target in Neuronal Damage and Prostate Cancer. EMBO J. 25, 1375-1384..
    
    
  
  
• Serine racemase from human brain: an unexpected role for a D-amino acid in the central nervous system
  
  
  • Stříšovský et al. (2005). Dual substrate and reaction specificity in mouse serine racemase: Identification of high-affinity dicarboxylate substrate and inhibitors and analysis of the ?-eliminase activity. Biochemistry 44, 13091-13100.
    
    
  • Stříšovský (2003). Mouse brain serine racemase catalyzes specific elimination of L-Ser to pyruvate. FEBS Lett. 535, 44-48.