|
|
|
Professor Jan Potempa
Department of Biotechnology
Jagiellonian University
ul. Gronostajowa 7, 30-387 Krakow, POLAND
Email: Potempa@uga.edu
Tel: http://www.mol.uj.edu.pl/staff/potempa/
Fax:
Homepage:
| Research |
We are interested in all aspects of participation of microbial proteases in pathogenicity of bacterial infections. These include the search, both at protein and genomic level, for new proteases which may be considered as virulence factors in several bacterial species. Our current work is focused on Porphyromonas gingivalis and Staphylococcus aureus. From the former species, several proteases have been purified and characterized. The major ones, referred to as gingipains, are cysteine proteases of caspase-like fold. They are implicated as important deterrents of the host antimicrobial defense system. Together with other proteases, including cysteine proteases related to streptopain or papain and several serine di- and tri-peptidyl peptidases, gingipains participate in nutrient acquisition by this bacterium responsible for the initiation and/or progression of periodontitis.
S. aureus secretes several proteases, amongst others, two extracellular cysteine peptidases of papain-like fold referred to as staphopains. They are secreted in the zymogen form with profragments working as inhibitors of the mature enzymes. Structurally, staphopains are closely related to cathepsin B, but enzyme specificity is either very unique (staphopain B) or related to cathepsin H (staphopain A). Apparently, the staphopains impose a serious and present danger for the cells producing them and are important virulence factors, since their activity is controlled at many levels, including multifactorial gene transcription regulation, cascade-like proteolytic processing of secreted proenzymes and, finally, staphopain inhibition by very specific inhibitors, staphostatins. Excitingly, the production of staphostatins, which are substrate-like binding staphopain inhibitors of a lipocalin-like fold that are necessary for maintenance of S. aureus cell wall structure.
|
|
| Collaborations |
|
|
| Publications |
Eichinger, A.,. Beisel, H.-G., Jacob, U., Huber, R., Medrano, F.-J., Banbula, A., Potempa, J., Travis, J., & Bode, W (1999) Crystal structure of gingipain R: a cysteine proteinase acting as the key virulence factor of periodontitis. EMBO J. 18: 5453-5462.
Lourbakos, A., Yuan, Y, Jenkins, A., Travis, J., Andre-Gordon, P., Santulli, R., Potempa, J., & Pike, R.N. (2001) Activation of proteinase activated receptors by gingipains from Porphyromonas gingivalis leads to platelet aggregation: A new trait in microbial pathogenesis. Blood 97: 3790-3797
Mikolajczyk, J., Boatright, K.M., Stennicke, H.R., Nazif, T., Potempa, J., Bogyo, M., and Salvesen, G.S. (2003) Sequential autolytic processing activates the zymogen of Arg-gingipain. J. Biol. Chem. 278: 10458-10464
Rzychon, M., Sabat, A., Kosowska, K., Potempa, J., Dubin, A. (2003) Staphostatins: an expanding new group of proteinase inhibitors with a unique specificity for the regulation of staphopains, Staphylococcus spp. cysteine proteinases. Mol. Microbiol. 49, 1051-1066
Filipek, R., Rzychon, M., Oleksy, A., Gruca, M., Dubin, A., Potempa, J., & Bochtler, M. (2003) The staphostatin-staphopain complex:a forward binding inhibitor in complex with its target cysteine protease. J. Biol Chem. 278: 40959-40966.
|
|
|
|
|
|
|
|
|
