dr hab. Beata Wielgus-Kutrowska

Zakład Biofizyki
Instytut Fizyki Doświadczalnej
Uniwersytet Warszawski
Pasteura 5, 02-093 Warszawa

Telefon: +48 22 5532339

E-mail: Beata.Wielgus-Kutrowska@fuw.edu.pl

Tematyka badawcza

I. Struktura i molekularny mechanizm działania enzymu - fosforylazy nukleozydów purynowych, badania krystalograficzne i w roztworze.

II. Zwijanie i agregacja białek.

Współpraca z Agnieszką Bzowską, Patrycją Clark (University of Notre Dame, USA), Andrzejem Sienkiewiczem (EPFL, Szwajcaria) i Michałem Żółkiewskim (Kansas State University, USA).

Wykształcenie i doświadczenie zawodowe

1993 Magister fizyki w zakresie biofizyki, Wydział Fizyki, Uniwersytet Warszawski
1993-1998 Studia doktoranckie, Zakład Biofizyki, Instytut Fizyki Doświadczalnej, Uniwersytet Warszawski
1999 Doktor fizyki w zakresie biofizyki, Wydział Fizyki, Uniwersytet Warszawski
2000 - Zakład Biofizyki, Instytut Fizyki Doświadczalnej, Uniwersytet Warszawski, adiunkt
2015 Doktor habilitowany w dziedzinie fizyki, w zakresie biofizyki, Wydział Fizyki, Uniwersytet Warszawski
1996-2001 Krótkie pobyty badawcze w laboratorium prof. Wolframa Saengera, Institut für Kristallographie, Freie Universität Berlin
2003 Staż podoktorski w laboratorium prof. Patricii Clark, University of Notre Dame, Notre Dame, Indiana, USA
2007-2015 Krótkie pobyty badawcze w laboratorium dr hab. Andrzeja Sienkiewicza, École polytechnique fédérale de Lausanne (EPFL), Szwajcaria
2012 Staż w laboratorium prof. Michała Żółkiewskiego, Kansas State University, Kansas, USA

Publikacje (1996-2015)

  1. H. Zhao, R. Ghirlando, C. Alfonso, F. Arisaka, I. Attali, D.L. Bain, M.M. Bakhtina, D.F. Becker, G.J. Bedwell, A. Bekdemir, T.M.D. Besong, C. Birck, C.A. Brautigam, W. Brennerman, O. Byron, A. Bzowska, J.B. Chaires, C.T. Chaton, H. Cölfen, K.D. Connaghan, K.A. Crowley, U. Curth, T. Daviter, W.L. Dean, A.I. Díez, C. Ebel, D.M. Eckert, L.E. Eisele, E. Eisenstein, P. England, C. Escalante, J.A. Fagan, R. Fairman, R.M. Finn, W. Fischle, J.G. de la Torre, J. Gor, H. Gustafsson, D. Hall, S.E. Harding, J.G. Hernández Cifre, A.B. Herr, E.E. Howell, R.S. Isaac, S.C. Jao, D. Jose, S.J. Kim, B. Kokona, J.A. Kornblatt, D. Kosek, E. Krayukhina, D. Krzizike, E.A. Kusznir, H. Kwon, A. Larson, T.M. Laue, A. Le Roy, A.P. Leech, H. Lilie, K. Luger, J.R. Luque-Ortega, J. Ma, C.A. May, E.L. Maynard, A. Modrak-Wojcik, Y.F. Mok, N. Mücke, L. Nagel-Steger, G.J. Narlikar, M. Noda, A. Nourse, T. Obsil, C.K. Park, J.K. Park, P.D. Pawelek, E.E. Perdue, S.J. Perkins, M.A. Perugini, C.L. Peterson, M.G. Peverelli, G. Piszczek, G. Prag, P.E. Prevelige, B.D.E. Raynal, L. Rezabkova, K. Richter, A.E. Ringel, R. Rosenberg, A.J. Rowe, A.C. Rufer, D.J. Scott, J.G. Seravalli, A.S. Solovyova, R. Song, D. Staunton, C. Stoddard, K. Stott, H.M. Strauss, W.W. Streicher, J.P. Sumida, S.G. Swygert, R.H. Szczepanowski, I. Tessmer, R.T. Toth, A. Tripathy, S. Uchiyama, S.F.W. Uebel, S. Unzai, A.V. Gruber, P.H. von Hippel, C. Wandrey, S.H. Wang, S.E. Weitzel, B. Wielgus-Kutrowska, C. Wolberger, M. Wolff, E. Wright, Y.S. Wu, J.M. Wubben, P. Schuck, A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation, PLoS One. 10:e0126420 (2015).
  2. J. Krasowska, K.G.Uriginov, P.L. Clark, A. Sienkiewicz, A. Bzowska, B. Wielgus-Kutrowska, Spectroscopic properties of two single-cysteine mutants of EGFP: C48S-EGFP and C70S-EGFP, Biomed. Spectr. Imag. 3, 231-236 (2014).
  3. B. Bertoša, G. Mikleušević, B. Wielgus-Kutrowska, M. Narczyk, M. Hajnić, I. Leščić Ašler, S. Tomić, M. Luić, A. Bzowska, Homooligomerization is needed for stability: a molecular modelling and solution study of Escherichia coli purine nucleoside phosphorylase, FEBS J. 281, 1717–1930 (2014).
  4. J. Wierzchowski, A. Stachelska-Wierzchowska, B. Wielgus-Kutrowska, G. Mikleušević, Two fluorogenic substrates for purine nucleoside phosphorylase, selective for mammalian and bacterial forms of the enzyme, Anal. Biochem. 446, 25-27 (2014).
  5. A. Stachelska-Wierzchowska, J. Wierzchowski, B. Wielgus-Kutrowska, G. Mikleušević, Enzymatic synthesis of highly fluorescent 8-azapurine ribosides using a purine nucleoside phosphorylase reverse reaction: variable ribosylation sites, Molecules 18, 12587-12598 (2013).
  6. B.Wielgus-Kutrowska, A. Modrak-Wójcik, A. Dyzma, K. Breer, M. Żółkiewski, A. Bzowska, Purine nucleoside phosphorylase activity decline is related to the decay of the enzyme in the trimeric form, Arch. Biochem. Biophys 549, 40–48, (2014).
  7. B. Wielgus-Kutrowska, A. Modrak-Wójcik, A. Dyzma, M. Żółkiewski, A. Bzowska, Inactivation of trimeric purine nucleoside phosphorylase: analytical ultracentrifugation studies, Europ. Biophys. J. 42, Suppl 1, S72 (2013).
  8. Z. Stefanić, G. Mikleusević, M. Narczyk, B. Wielgus-Kutrowska, A. Bzowska, M. Luić, Still a long way to fully understanding the molecular mechanism of Escherichia coli purine nucleoside phosphorylase, Croat. Chem. Acta 86, 117-127 (2013).
  9. Z. Stefanic, M. Narczyk, G. Mikleusevic, B. Wielgus-Kutrowska, A. Bzowska, M. Luic, New phosphate binding sites in the crystal structure of Escherichia coli purine nucleoside phosphorylase complexed with phosphate and formycin A, FEBS Letters 586, 967-971 (2012).
  10. B.Wielgus-Kutrowska, K. Breer, M. Hashimoto, S. Hikishima, T. Yokomatsu, A. Dyzma, M. Narczyk, A. Girstun, K. Staroń, A. Bzowska, Trimeric purine nucleoside phosphorylase: exploring postulated one-third-of-the-sites binding in the transition-state, Bioorg Med Chem. 20, 6758-6769 (2012).
  11. G. Mikleusević, Z. Stefanić, M. Narczyk, B. Wielgus-Kutrowska, A. Bzowska, M. Luić, Validation of the catalytic mechanism of Escherichia coli purine nucleoside phosphorylase by structural and kinetic studies, Biochimie 93, 1610-1622 (2011).
  12. K. Breer, L. Glava1-Obrovac, M. Suver, S. Hikishima, M. Hashimoto, T. Yokomats, B. Wielgus-Kutrowska, L. Magnowska, A. Bzowska, 9-Deazaguanine derivatives connected by a linker to difluoromethylene phosphonic acid are slow-binding picomolar inhibitors of trimeric purine nucleoside phosphorylase, FEBS Journal 277, 1747-1760 (2010).
  13. J. Krasowska, M. Olasek, A. Bzowska, . L. Clark, B. Wielgus-Kutrowska, The comparison of aggregation and folding of enhanced green fluorescent protein (EGFP) by spectroscopic studies, Spectroscopy 24, 343-348 (2010).
  14. K. Breer, B. Wielgus-Kutrowska, A. Girstun, K. Staron, M. Hashimoto, S. Hikishima, T. Yokomatsu, A. Bzowska, Overexpressed proteins may act as mops removing their ligands from the host cells: a case study of calf PNP, BBRC, 391, 1203-1209 (2010).
  15. G. Chojnowski, K. Breer, M. Narczyk, B. Wielgus-Kutrowska, H. Czapinska, M. Hashimoto, S. Hikishima, T. Yokomatsu, M. Bochtler, A. Girstun, K. Staron, A. Bzowska, 1.45 . resolution crystal structure of recombinant PNP in complex with a pM multisubstrate analogue inhibitor bearing one feature of the postulated transition state, BBRC, 391, 703-708 (2010).
  16. J. Antosiewicz, K Breer, A. Bzowska, B. Wielgus-Kutrowska, On the analysis of fluorimetric titration curves of purine nucleoside phosphorylase. Nucleic Acids Symp Ser (Oxf) 52, 671-672 (2008).
  17. K. Breer, B. Wielgus-Kutrowska, M. Hashimoto, S. Hikishima, T. Yokomatsu, R.H. Szczepanowski, M. Bochtler, A. Girstun, K. Staron, A. Bzowska, Thermodynamic studies of interactions of calf spleen PNP with acyclic phosphonate inhibitors. Nucleic Acids Symp Ser (Oxf) 52, 663-664 (2008).
  18. K Breer, A. Girstun, B. Wielgus-Kutrowska, K. Staroń, A. Bzowska, Overexpression, purification and characterization of functional calf purine nucleoside phosphorylase (PNP). Protein Expr Purif. 61, 122-130 (2008).
  19. K Stepniak, A. Girstun, B. Wielgus-Kutrowska, K. Staroń, A. Bzowska, Cloning, expression, purification, and some properties of calf purine nucleoside phosphorylase. Nucleosides Nucleotides Nucleic Acids 6-7, 855-859 (2007).
  20. J.M. Antosiewicz, B. Wielgus-Kutrowska, M. Długosz, A. Holy, A. Bzowska, Kinetics of binding of multisubstrate analogue inhibitor (2-amino-9-[2-(phosphonomethoxy)ethyl]-6-sulfanylpurine) with trimeric purine nucleoside phosphorylase. Nucleosides Nucleotides Nucleic Acids 8-9, 969-974 (2007).
  21. B. Wielgus-Kutrowska, M. Narczyk. A. Buszko, A. Bzowska, P. Clark, Folding and unfolding of non-fluorescent mutant of green fluorescent protein. J. Phys.: Condens. Matter 19, 285223 (2007).
  22. B. Wielgus-Kutrowska, J. Antosiewicz, M. Długosz, A. Holý, A. Bzowska, Towards the mechanism of trimeric purine nucleoside phosphorylases: stopped-flow studies of binding of multisubstrate analogue inhibitor - 2-amino-9-[2-(phosphonomethoxy)-ethyl]-6-sulfanylpurine. Biophys. Chem. 125, 260-268 (2007).
  23. B. Wielgus-Kutrowska, A. Bzowska, Probing the mechanism of purine nucleoside phosphorylase by steady-state kinetic studies and ligand binding characterization determined by fluorimetric titrations. Biochim. Biophys. Acta 1764, 887-902 (2006).
  24. B. Wielgus-Kutrowska, A. Bzowska, Kinetic properties of Cellulomonas sp. purine nucleoside phosphorylase with typical and non-typical substrates: implications for the reaction mechanism. Nucleosides, Nucleotides and Nucleic Acids 5-7, 471-476 (2005).
  25. A. Bzowska, K. Stepniak, M. Olasek, M. Długosz, B. Wielgus-Kutrowska, J. Antosiewicz, A. Holy, G. Koellner, A. Stroh, G. Raszewski, T. Steiner and J. Frank, Attemps to differentiate subunits of trimeric and hexameric purine nucleoside phosphorylase by crystal structure and solution studies using purine bases, modified purine nucleosides, acyclonucleosides and their phoshonate analogues. Chemistry of Nucleic Acid Components, Collection Symposium Series, vol. 7, 133-142 (2005).
  26. A. Bzowska, G. Koellner, B. Wielgus-Kutrowska, A. Stroh, G. Raszewski, A. Holý, T. Steiner, J. Frank, Crystal structure of calf spleen purine nucleoside phosphorylase with two full trimers in the asymmetric unit: important implications for the mechanism of catalysis. J. Mol. Biol. 342, 1015-1032 (2004).
  27. B. Wielgus-Kutrowska, A. Holy, J. Frank, G. Koellner and A. Bzowska, Interactions of trimeric purine nucleoside phosphorylases with ground state analogues - calorimetric and fluorimetric studies. Nucleosides, Nucleotides and Nucleic Acids 22, 1695-1698 (2003).
  28. B. Wielgus-Kutrowska, A. Bzowska, J. Tebbe, G. Koellner and D. Shugar, Purine nucleoside phosphorylase from Cellulomonas sp.: physicochemical properties and binding of substrates determined by ligand-dependent enhancement of enzyme intrinsic fluorescence, and by protective effects of ligands on thermal inactivation of the enzyme. Biochim. Biophys. Acta 1597, 320-334 (2002).
  29. G. Koellner, A. Bzowska, B. Wielgus-Kutrowska, M. Luić, T. Steiner, W. Saenger and J. Stępiński, Open and closed conformation of the E. coli purine nucleoside phosphorylase active center and implications for the catalytic mechanism. J. Mol. Biol. 315, 351-371 (2002).
  30. B. Wielgus-Kutrowska, J. Tebbe, J. Wierzchowski, D. Shugar, W. Saenger, G. Koellner and A. Bzowska, Binding of substrates by purine nucleoside phosphorylase (PNP) from Cellulomonas sp. - kinetic and spectrofluorimetric studies. Nucleosides and Nucleotides 18, 871-872 (1999).
  31. J. Tebbe, A. Bzowska, B. Wielgus-Kutrowska, W. Schröder, Z. Kazimierczuk, D. Shugar, W. Saenger, W. and G. Koellner, Crystal structures of purine nucleoside phosphorylase (PNP) from Cellulomonas sp. and its implications of the molecular mechanism of trimeric PNPs. J. Mol. Biol. 294, 1239-1255 (1999).
  32. A. Bzowska, L. Magnowska, B. Wielgus-Kutrowska and Z. Kazimierczuk, Synthesis of 2-chloro-6-aryloxy- and 2-chloro-6-alkoxyarylpurines and their properties in purine nucleoside phosphorylase (PNP) system. Nucleos. And Nucleot.18 (4-5), 873-874 (1999).
  33. B. Wielgus-Kutrowska, J. Tebbe, W. Schröder, M. Luič, D. Shugar, W. Saenger, G. Koellener and A. Bzowska, Cellulomonas sp. Purine Nucleoside Phosphorylase (PNP): Comparison with Human and E. Coli Enzymes. Adv. Exp. Med. Biol. 431, 259-264, Plenum Publishing Corp., New York (1998) .
  34. A. Bzowska, J. Tebbe, M. Luič, B. Wielgus-Kutrowska, W. Schröder, D. Shugar, W. Saenger, and G. Koellener, Crystallization and preliminary studies of purine nucleoside phosphorylase from Cellulomonas sp. Acta Cryst. D54, 1061-1063 (1998).
  35. B. Wielgus-Kutrowska, E. Kulikowska, J. Wierzchowski,A. Bzowska and D. Shugar, Nicotinamide riboside - an unusual, non-typical substrate of purified purine nucleoside phosphorylases. Eur. J. Biochem. 243, 408-414 (1997).
  36. J. Wierzchowski, B. Wielgus-Kutrowska and D. Shugar, Fluorescence emission of 8-azapurines and their nucleosides, and application to the kinetic reverse synthetic reaction of purine nucleoside phosphorylase. Biochim. Biophys. Acta 1290, 9-17 (1996).
  37. J. Tebbe, B. Wielgus-Kutrowska, W. Schröder, M. Luič, D. Shugar, W. Saenger, G. Koellener and A. Bzowska, Purine nucleoside phosphorylase (PNP) from Cellulomonas sp., a third class of PNP different from both "low-molecular weight" mammalian and "high-molecular weight" bacterial PNPs. Miami, Nature Biotechnology, Short Reports, Vol. 8, p. 90, Oxford University Press (1996).

Udział w projektach

Biofizyczne podstawy działania fosforylaz nukleozydów purynowych oraz synteza i badania biologiczne ich inhibitorów o potencjalnym znaczeniu farmakologicznym

Fałdowanie de novo białka zielonej fluorescencji (GFP) w aspekcie zastosowań w biotechnologii i biologii molekularnej

Enzymy homooligomeryczne o bardzo silnej (nieskonczonej) negatywnej kooperacji w wiązaniu ligandów i katalizie: czy natura jest rozrzutna?

Zakład Biofizyki, Instytut Fizyki Doświadczalnej, Wydział Fizyki, Uniwersytet Warszawski, ul. Pasteura 5, 02-093 Warszawa
Email: office@biogeo.uw.edu.pl :: Telefon: +48 22 5532304