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Start Over Author "Potempa, Jan" Journal journal of biological chemistry
45 results on '"Potempa, Jan"'

2. Mammalian-like type II glutaminyl cyclases in Porphyromonas gingivalis and other oral pathogenic bacteria as targets for treatment of periodontitis

Author

Taudte, Nadine, primary, Linnert, Miriam, additional, Rahfeld, Jens-Ulrich, additional, Piechotta, Anke, additional, Ramsbeck, Daniel, additional, Buchholz, Mirko, additional, Kolenko, Petr, additional, Parthier, Christoph, additional, Houston, John A., additional, Veillard, Florian, additional, Eick, Sigrun, additional, Potempa, Jan, additional, Schilling, Stephan, additional, Demuth, Hans-Ulrich, additional, and Stubbs, Milton T., additional

Published
2021
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5. Structural insights unravel the zymogenic mechanism of the virulence factor gingipain K from Porphyromonas gingivalis, a causative agent of gum disease from the human oral microbiome

Author

Pomowski, Anja, primary, Usón, Isabel, additional, Nowakowska, Zuzanna, additional, Veillard, Florian, additional, Sztukowska, Maryta N., additional, Guevara, Tibisay, additional, Goulas, Theodoros, additional, Mizgalska, Danuta, additional, Nowak, Magdalena, additional, Potempa, Barbara, additional, Huntington, James A., additional, Potempa, Jan, additional, and Gomis-Rüth, F. Xavier, additional

Published
2017
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6. Structure and mechanism of cysteine peptidase gingipain K (Kgp), a major virulence factor of porphyromonas gingivalis

Author

Diego, Iñaki de, Veillard, Florian T., Sztukowska, Maryta, Guevara, Tibisay, Potempa, Barbara, Pomowski, Anja, Huntington, James Andrew, Potempa, Jan, Gomis-Rüth, F. Xavier, National Institutes of Health (US), National Science Centre (Poland), Ministry of Science and Higher Education (Poland), European Commission, Ministerio de Economía y Competitividad (España), Ministerio de Educación y Ciencia (España), and Generalitat de Catalunya

Abstract

© 2014 by The American Society for Biochemistry and Molecular Biology Inc. Cysteine peptidases are key proteolytic virulence factors of the periodontopathogen Porphyromonas gingivalis, which causes chronic periodontitis, the most prevalent dysbiosisdriven disease in humans. Two peptidases, gingipain K (Kgp) and R (RgpA and RgpB), which differ in their selectivity after lysines and arginines, respectively, collectively account for 85% of the extracellular proteolytic activity of P. gingivalis at the site of infection. Therefore, they are promising targets for the design of specific inhibitors. Although the structure of the catalytic domain of RgpB is known, little is known about Kgp, which shares only 27% sequence identity. We report the high resolution crystal structure of a competent fragment of Kgp encompassing the catalytic cysteine peptidase domain and a downstream immunoglobulin superfamily-like domain, which is required for folding and secretion of Kgp in vivo. The structure, which strikingly resembles a tooth, was serendipitously trapped with a fragment of a covalent inhibitor targeting the catalytic cysteine. This provided accurate insight into the active site and suggested that catalysis may require a catalytic triad, Cys477-His444-Asp388, rather than the cysteine-histidine dyad normally found in cysteine peptidases. In addition, a 20-Å-long solventfilled interior channel traverses the molecule and links the bottom of the specificity pocket with the molecular surface opposite the active site cleft. This channel, absent in RgpB, may enhance the plasticity of the enzyme, which would explain the much lower activity in vitro toward comparable specific synthetic substrates. Overall, the present results report the architecture and molecular determinants of the working mechanism of Kgp, including interaction with its substrates., This work was supported, in whole or in part, by National Institutes of Health Grant DE09761/DE/NIDCR. This work was also supported by Polish National Science Center Grant UMO-2012/04/A/NZ1/00051; Ministry of Science and Higher Education of Poland Grant 2137/7.PR-EU/2011/2; European Union Grants FP7-HEALTH-2010-261460 “Gums&Joints,” FP7-PEOPLE-2011-ITN-290246 “RAPID,” FP7-HEALTH-2012-306029-2 “TRIGGER,” and POIG.02.01.00-12-064/08; Spanish Ministry of Economy and Competitiveness Grants BFU2012-32862 and BIO2013-49320-EXP; Spanish Ministry of Science and Education Grant CSD2006-00015; and National Government of Catalonia Grant 2014SGR9. Funding for data collection was provided in part by the European Synchrotron Radiation Facility (Grenoble, France)

Published
2014

7. Gingipains of Porphyromonas gingivalis Affect the Stability and Function of Serine Protease Inhibitor of Kazal-type 6 (SPINK6), a Tissue Inhibitor of Human Kallikreins

Author

Plaza, Karolina, primary, Kalinska, Magdalena, additional, Bochenska, Oliwia, additional, Meyer-Hoffert, Ulf, additional, Wu, Zhihong, additional, Fischer, Jan, additional, Falkowski, Katherine, additional, Sasiadek, Laura, additional, Bielecka, Ewa, additional, Potempa, Barbara, additional, Kozik, Andrzej, additional, Potempa, Jan, additional, and Kantyka, Tomasz, additional

Published
2016
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13. Staphylococcal SplB Serine Protease Utilizes a Novel Molecular Mechanism of Activation

Author

Pustelny, Katarzyna, primary, Zdzalik, Michal, additional, Stach, Natalia, additional, Stec-Niemczyk, Justyna, additional, Cichon, Przemyslaw, additional, Czarna, Anna, additional, Popowicz, Grzegorz, additional, Mak, Pawel, additional, Drag, Marcin, additional, Salvesen, Guy S., additional, Wladyka, Benedykt, additional, Potempa, Jan, additional, Dubin, Adam, additional, and Dubin, Grzegorz, additional

Published
2014
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14. Porphyromonas gingivalis-derived Lysine Gingipain Enhances Osteoclast Differentiation Induced by Tumor Necrosis Factor-α and Interleukin-1β but Suppresses That by Interleukin-17A

Author

Akiyama, Tomohito, primary, Miyamoto, Yoichi, additional, Yoshimura, Kentaro, additional, Yamada, Atsushi, additional, Takami, Masamichi, additional, Suzawa, Tetsuo, additional, Hoshino, Marie, additional, Imamura, Takahisa, additional, Akiyama, Chie, additional, Yasuhara, Rika, additional, Mishima, Kenji, additional, Maruyama, Toshifumi, additional, Kohda, Chikara, additional, Tanaka, Kazuo, additional, Potempa, Jan, additional, Yasuda, Hisataka, additional, Baba, Kazuyoshi, additional, and Kamijo, Ryutaro, additional

Published
2014
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15. Three-dimensional structure of MecI. Molecular basis for transcriptional regulation of staphylococcal methicillin resistance

Author

García-Castellanos, Raquel, Marrero, Aniebrys, Mallorquí-Fernández, Goretti, Potempa, Jan, Coll, Miquel, and Gomis-Rüth, F. Xavier

Subjects
Antibiotics, Cells, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, Biosynthesis, Dimers
Abstract

Methicillin-resistant Staphylococcus aureus is the main cause of nosocomial and community-onset infections that affect millions of people worldwide. Some methicillin-resistant Staphylococcus aureus infections have become essentially untreatable by β-lactams because of acquired molecular machineries enabling antibiotic resistance. Evasion from methicillin challenge is mainly achieved by the synthesis of a penicillin-binding protein of low affinity for antibiotics, MecA, that replaces regular penicillin-binding proteins in cell wall turnover when these have been inactivated by antibiotics. MecA synthesis is regulated by a signal transduction system consisting of the sensor/transducer MecR1 and the 14-kDa transcriptional repressor MecI (also known as methicillin repressor) that constitutively blocks mecA transcription. The three-dimensional structure of MecI reveals a dimer of two independent winged helix domains, each of which binds a palindromic DNA-operator half site, and two intimately intertwining dimerization domains of novel spiral staircase architecture, held together by a hydrophobic core. Limited proteolytic cleavage by cognate MecR1 within the dimerization domains results in loss of dimer interaction surface, dissociation, and repressor release, which triggers MecA synthesis. Structural information on components of the MecA regulatory pathway, in particular on methicillin repressor, the ultimate transcriptional trigger of mecA-encoded methicillin resistance, is expected to lead to the development of new antimicrobial drugs., This work was supported in part by Spanish Ministry for Science and Technology Grants BIO2000-1659 and BIO2003-00132 (to F. X. G. R.) and BIO2002-00379 (to M. C.) and Grant SGR2001-00346 from the Generalitat de Catalunya (to M. C.)

Published
2003

17. Site-specific O-Glycosylation on the MUC2 Mucin Protein Inhibits Cleavage by the Porphyromonas gingivalis Secreted Cysteine Protease (RgpB)

Author

van der Post, Sjoerd, primary, Subramani, Durai B., additional, Bäckström, Malin, additional, Johansson, Malin E.V., additional, Vester-Christensen, Malene B., additional, Mandel, Ulla, additional, Bennett, Eric P., additional, Clausen, Henrik, additional, Dahlén, Gunnar, additional, Sroka, Aneta, additional, Potempa, Jan, additional, and Hansson, Gunnar C., additional

Published
2013
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18. A New Autocatalytic Activation Mechanism for Cysteine Proteases Revealed by Prevotella intermedia Interpain A

Author

Mallorquí-Fernández, Noemí, primary, Manandhar, Surya P., additional, Mallorquí-Fernández, Goretti, additional, Usón, Isabel, additional, Wawrzonek, Katarzyna, additional, Kantyka, Tomasz, additional, Solà, Maria, additional, Thøgersen, Ida B., additional, Enghild, Jan J., additional, Potempa, Jan, additional, and Gomis-Rüth, F. Xavier, additional

Published
2008
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22. The Staphostatin-Staphopain Complex

Author

Filipek, Renata, primary, Rzychon, Malgorzata, additional, Oleksy, Aneta, additional, Gruca, Milosz, additional, Dubin, Adam, additional, Potempa, Jan, additional, and Bochtler, Matthias, additional

Published
2003
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40. The Clostridium ramosumIgA Proteinase Represents a Novel Type of Metalloendopeptidase*

Author

Kosowska, Klaudia, Reinholdt, Jesper, Rasmussen, Lone Kjær, Sabat, Artur, Potempa, Jan, Kilian, Mogens, and Poulsen, Knud

Abstract

Clostridium ramosumis part of the normal flora in the human intestine. Some strains produce an IgA proteinase that specifically cleaves human IgA1 and the IgA2m(1) allotype. This prolylendopeptidase was purified from a broth culture supernatant, and N-terminal sequences of the native protein and tryptic fragments thereof were determined. A fragment of the igagene encoding the IgA proteinase was isolated using degenerate primers in PCR, and the complete gene was obtained by inverse PCR. The identity of the igagene was confirmed by heterologous expression in Escherichia coli. The deduced amino acid sequence indicated a signal peptide of 30 residues and a secreted proteinase of 133,828 Da. A typical Gram-positive cell wall anchor motif was identified in the C terminus. The presence of a putative zinc-binding motif His-Glu-Phe-Gly-His together with inhibition studies indicate that the proteinase belongs to the zinc-dependent metalloproteinases. However, the sequence of the C. ramosumIgA proteinase shows no overall similarity to other proteins except for significant identity around the zinc-binding motif with family M6 of metalloendopeptidases, and the unique sequence of the IgA proteinase in this area presumably establishes a new subfamily. The GC percentage of the igagene is significantly higher than that for the entire genome of C. ramosum, suggesting that the gene was acquired recently in evolution.

Published
2002
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41. Loss of Clumping Factor B Fibrinogen Binding Activity byStaphylococcus aureusInvolves Cessation of Transcription, Shedding and Cleavage by Metalloprotease*

Author

McAleese, Fionnuala M., Walsh, Evelyn J., Sieprawska, Magdalena, Potempa, Jan, and Foster, Timothy J.

Abstract

The fibrinogen-binding protein clumping factor B (ClfB) of Staphylococcus aureusis present on the surface of cells from the early exponential phase of growth in greater amounts than on cells from late exponential phase and is barely detectable on cells from stationary phase. Expression of a clfB-lacZfusion indicated that transcription stopped before the end of exponential phase. Mutations in the global regulators agrand sarhad no effect on clfBtranscription. The loss of ClfB protein from cells in stationary phase was due to expression ending before cells stopped growing, combined with shedding of some of the protein into the growth medium and dilution of those molecules remaining on the cell surface during the two to three cell division events leading to stationary phase. Two forms of the protein occurred on the cell surface, the smaller of which was generated by loss of a domain from the N terminus. The proportion of the smaller form increased as the cultures grew. The metalloprotease aureolysin was shown to be responsible for cleavage of ClfB. Cleavage was inhibited by EDTA and o-phenanthroline and did not occur in an aureolysin-deficient mutant. Purified aureolysin promoted cleavage of cell surface-located ClfB as well as the recombinant A domain of ClfB. Cleavage was detected at two sites, one located between residues Ser197and Leu198and the other between Ala199and Val200. The truncated form of ClfB did not bind fibrinogen.

Published
2001
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42. Porphyromonas gingivalisDPP-7 Represents a Novel Type of Dipeptidylpeptidase*

Author

Banbula, Agnieszka, Yen, Jane, Oleksy, Aneta, Mak, Pawel, Bugno, Marcin, Travis, James, and Potempa, Jan

Abstract

A novel dipeptidylpeptidase (DPP-7) was purified from the membrane fraction of Porphyromonas gingivalis.This enzyme, with an apparent molecular mass of 76 kDa, has the specificity for both aliphatic and aromatic residues in the P1 position. Although it belongs to the serine class of peptidases, it does not resemble other known dipeptidylpeptidases. Interestingly, the amino acid sequence around the putative active site serine residue shows significant similarity to the C-terminal region of theStaphylococcus aureusV-8 endopeptidase. The genes encoding homologues of DPP-7 were found in genomes of Xylella fastidiosa, Shewanella putrefaciens, andP. gingivalis.It is likely that at least in P. gingivalis, DPP-7 and its homologue, in concert with other di- and tripeptidases, serve nutritional functions by providing dipeptides to this asaccharolytic bacterium.

Published
2001
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43. Molecular Cloning and Characterization of Porphyromonas gingivalisLysine-specific Gingipain

Author

Pavloff, Nadine, Pemberton, Philip A., Potempa, Jan, Chen, Wan-Ching Audrey, Pike, Robert N., Prochazka, Vaclav, Kiefer, Michael C., Travis, James, and Barr, Philip J.

Abstract

The proteinases of Porphyromonas gingivalisare key virulence factors in the etiology and progression of periodontal disease. Previous work in our laboratories resulted in the purification of arginine- and lysine-specific cysteine proteinases, designated gingipains, that consist of several tightly associated protein subunits. Recent characterization of arginine-specific gingipain-1 (gingipain R1; RGP-1) revealed that the sequence is unique and that the protein subunits are initially translated as a polyprotein encoding a proteinase domain and multiple adhesin domains (Pavloff, N., Potempa, J., Pike, R. N., Prochazka, V., Kiefer, M. C., Travis, J., and Barr, P. J. (1995) J. Biol. Chem.270, 1007-1010).

Published
1997
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44. A New Autocatalytic Activation Mechanism for Cysteine Proteases Revealed by Prevotella intermedia Interpain A.

Author

MaIIorquí-Fernández, Noemí, Manandhar, Surya P., MaIIorquí-Fernández, Goretti, Usón, Isabel, Wawrzonek, Katarzyna, Kantyka, Tomasz, SoIà, Maria, Thøgersen, Ida B., Enghild, Jan J., Potempa, Jan, and Gomis-Rüth, F. Xavier

Subjects
*CYSTEINE proteinases, *PERIODONTITIS, *TRYPTOPHAN, *PATHOGENIC microorganisms, *PORPHYROMONAS gingivalis
Abstract

Prevotella intermedia is a major periodontopathogen contributing to human gingivitis and periodontitis. Such pathogens release proteases as virulence factors that cause deterrence of host defenses and tissue destruction. A new cysteine protease from the cysteine-histidine-dyad class, interpain A, was studied in its zymogenic and self-processed mature forms. The latter consists of a bivalved moiety made up by two subdomains. In the structure of a catalytic cysteine-to-alanine zymogen variant, the right subdomain interacts with an unusual prodomain, thus contributing to latency. Unlike the catalytic cysteine residue, already in its competent conformation in the zymogen, the catalytic histidine is swung out from its active conformation and trapped in a cage shaped by a backing helix, a zymogenic hairpin, and a latency flap in the zymogen. Dramatic rearrangement of up to 20 Å of these elements triggered by a tryptophan switch occurs during activation and accounts for a new activation mechanism for proteolytic enzymes. These findings can be extrapolated to related potentially pathogenic cysteine proteases such as Streprococcuspyogenes SpeB and Porphyromonas gingivalis periodontain. [ABSTRACT FROM AUTHOR]

Published
2008
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45. Sequential Autolytic Processing Activates the Zymogen of Arg-gingipain.

Author

Mikolajczy, Jowita, Boatright, Kelly M., Stennicke, Henning R., Nazif, Tamim, Potempa, Jan, Bogyo, Matthew, and Salvesen, Guy S.

Subjects
*PORPHYROMONAS gingivalis, *AUTOLYSIS
Abstract

Expresses the full-length precursor of the Arg-specific caspase relative from the bacterium Porphyromonas gingivalis, Arg-gingipain-B, and shows that it contains N- and C-terminal extensions that render a low amount of latency. Substantially active zymogen; Requirement of three sequential autolytic processing steps at the N and C terminus for full activity; N-propeptide as intramolecular chaperone rather than an inhibitory peptide.

Published
2003
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