Structural Biology Laboratory

PROFILE

The laboratory is focused on the study of the structure, functions and mechanisms of the nucleoprotein complexes involved in the basic processes of DNA replication and repair. We investigate a number of systems in viral, bacterial, and human cells to understand the assembly of macromolecular complexes and use this knowledge in possible therapeutic strategies.

RESEARCH TEAM

Intercollegiate Faculty of Biotechnology of the UG & MUG
Core Facility Laboratories
Structural Biology Laboratory
Ul. Abrahama 58, 80-307 Gdańsk, POLAND

Group Leader:

Michal R. Szymanski, PhD
email:     michal.szymanski@ug.edu.pl
               michal.szymanski@biotech.ug.edu.pl
phone:   +48 58 523 6366
https://www.researchgate.net/profile/Michal_Szymanski2

Group Members:

Anna Karlowicz, PhD
Andrzej Dubiel, MSc

Currently open or soon to be open positions:

Interested and motivated candidates who wish to join our group (master, PhD or postdoc) please contact us for further details: michal.szymanski@ug.edu.pl

GRANTS

Project title Project Investigator Source of financing Amount Years
Targeting mitochondrial DNA repair for novel anti-cancer therapies  Szymański Michał R.  First TEAM 3 2 000 000,00 PLN 2018 - 2021
Unraveling the molecular basis of DNA damage recognition and processing in human mitochondria Szymański Michał R. POLONEZ 2 944 874,00 PLN 2017 - 2019

PUBLICATIONS

  1. Szymanski, M.R., Yu, A., Gmyrek, A.M., White, M.A., Molineux, I.J., Lee, J.C., Yin W.Y. A novel domain in human EXOG converts apoptotic endonuclease to DNA- repair exonuclease. Nature Communications. 2017 May 3;8:14959.
    Recommended by F1000.
  2. Li, M., Mislak, A.C., Foli, Y., Agbosu, E., Bose, V., Bhandari, S., Szymanski, M.R., Shumate, C.K., Yin, W., Anderson, K.S., Paintsil, E. DNA Polymerase-γ R953C Mutant Linked to ART-Associated Mitochondrial Toxicity. Antimicrobial Agents and Chemotherapy. 2016 Aug 22;60(9):5608-11.
  3. Sohl, C.D*., Szymanski, M.R*., Mislak, A.C., Shumate, K.C., Amiralaei, S., Schinazi, F.R., Anderson K.S., Yin W.Y. Probing the Structural and Molecular Basis of Nucleotide Selectivity by Human Mitochondrial DNA Polymerase γ. Proceedings of National Academy of Sciences of the United States of America. 2015 Jul 14;112(28):8596-601.
    *equal contribution
  4. Szymanski, M.R., Kuznetsov, V.B., Shumate, C., Meng, Q., Lee, Y-S., Patel, G., Patel, S.S., Yin W.Y. Structural basis for processivity and antiviral drug toxicity in human mitochondrial DNA replicase. EMBO J. 2015 Jul 14; 34(14):1959-70.
  5. Szymanski, M.R., Jezewska, M.J., Bujalowski, W. The Escherichia Coli Primosomal DnaT Protein Exists in Solution as a Monomer – Trimer Equilibrium System. Biochemistry. 2013 Mar 19;52(11):1845-57.
  6. Szymanski, M.R., Jezewska, M.J., Bujalowski, W. Energetics of the Escherichia Coli DnaT Protein Trimerization Reaction. Biochemistry. 2013 Mar 19;52(11):1858-73.
  7. Szymanski, M.R., Bujalowski, P.J., Jezewska, M.J., Gmyrek, A.M., and Bujalowski, W. The N-terminal domain of the Escherichia coli PriA helicase contains both the DNA- and nucleotide-binding sites. Energetics of domain-DNA interactions and allosteric effect of the nucleotide cofactors. Biochemistry. 2011 Nov 1;50(43):9167-83.
  8. Szymanski, M.R., Jezewska, M.J., and Bujalowski, W. Binding of Two PriAPriB Complexes to the Primosome Assembly Site Initiates Primosome Formation. Journal of Molecular Biology. 2011 Aug 5;411(1):123-42.
  9. Szymanski, M.R., Jezewska, M.J., Bujalowski, P.J., Bussetta, C., Ye, M., Choi K.H., Bujalowski, W. Full-Length Dengue Virus RNA Dependent RNA Polymerase – RNA/ DNA Complexes. Stoichiometries and Energetics of Intrinsic Affinities, Cooperativities, Base and Conformational Specificities. Journal of Biological Chemistry. 2011 Sep 23;286(38):33095-108.
  10. Jezewska, M.J., Szymanski, M.R., and Bujalowski, W. Kinetic mechanism of the ssDNA recognition by the polymerase X from African Swine Fever Virus. Dynamics and energetics of intermediate formations. Biophysical Chemistry. 2011 Sep;158(1):9-20.
  11. Jezewska, M.J., Szymanski, M.R., and Bujalowski, W. Interactions of the DNA polymerase X from African Swine Fever Virus with the ssDNA. Properties of the total DNA-binding site and the strong DNA-binding subsite. Biophysical Chemistry. 2011 Sep;158(1):26-37.
  12. Jezewska, M.J., Szymanski, M.R., and Bujalowski, W. The primary DNAbinding subsite of the rat pol beta. Energetics of interactions of the 8-kDa domain of the enzyme with the ssDNA. Biophysical Chemistry. 2011 Jul;156(2-3):115-27.
  13. Szymanski, M.R., Jezewska, M.J., and Bujalowski, W. The Escherichia coli PriA helicase-double-stranded DNA complex: location of the strong DNA-binding subsite on the helicase domain of the protein and the affinity control by the two nucleotide-binding sites of the enzyme. Journal of Molecular Biology. 2010 Sep 17;402(2):344-62.
  14. Szymanski, M.R., Jezewska, M.J., and Bujalowski, W. Interactions of the Escherichia coli primosomal PriB protein with the single-stranded DNA. Stoichiometries, intrinsic affinities, cooperativities, and base specificities. Journal of Molecular Biology. 2010 Apr 23;398(1):8-25.
  15. Szymanski, M.R., Jezewska, M.J., and Bujalowski, W. The Escherichia coli PriA helicase specifically recognizes gapped DNA substrates: effect of the two nucleotide-binding sites of the enzyme on the recognition process. Journal of Biological Chemistry. 2010 Mar 26;285(13):9683-96.
  16. Andreeva, I.E., Roychowdhury, A., Szymanski, M.R., Jezewska, M.J., and Bujalowski, W. Mechanisms of interactions of the nucleotide cofactor with the RepA protein of plasmid RSF1010. Binding dynamics studied using the fluorescence stopped-flow method. Biochemistry. 2009 Nov 10;48(44):10620-36.
  17. Szymanski, M.R., Fiebach, A.R., Tratschin, J.D., Gut, M., Ramanujam, V.M., Gottipati, K., Patel, P., Ye, M., Ruggli, N., and Choi, K.H. Zinc binding in pestivirus N(pro) is required for interferon regulatory factor 3 interaction and degradation. Journal of Molecular Biology. 2009 Aug 14;391(2):438-49.
  18. Roychowdhury, A., Szymanski, M.R., Jezewska, M.J., and Bujalowski, W. Interactions of the Escherichia coli DnaB-DnaC protein complex with nucleotide cofactors. 1. Allosteric conformational transitions of the complex. Biochemistry. 2009 Jul 28;48(29):6712-29.
  19. Roychowdhury, A., Szymanski, M.R., Jezewska, M.J., and Bujalowski, W. Mechanism of NTP hydrolysis by the Escherichia coli primary replicative helicase DnaB protein. 2. Nucleotide and nucleic acid specificities. Biochemistry. 2009 Jul 28;48(29):6730-46.
  20. Roychowdhury, A., Szymanski, M.R., Jezewska, M.J., and Bujalowski, W. Escherichia coli DnaB helicase-DnaC protein complex: allosteric effects of the nucleotides on the nucleic acid binding and the kinetic mechanism of NTP hydrolysis. 3. Biochemistry. 2009 Jul 28;48(29):6747-63.
  21. Andreeva, I.E., Szymanski, M.R., Jezewska, M.J., Galletto, R., and Bujalowski, W. Dynamics of the ssDNA recognition by the RepA hexameric helicase of plasmid RSF1010: analyses using fluorescence stopped-flow intensity and anisotropy methods. Journal of Molecular Biology. 2009 May 15;388(4):751-75.
  22. Duret, G., Szymanski, M., Choi, K.J., Yeo, H.J., and Delcour, A.H. The TpsB translocator HMW1B of haemophilus influenzae forms a large conductance channel. Journal of Biological Chemistry. 2008 Jun 6;283(23):15771-8.

COLLABORATIONS

Dr Bartosz Szczesny, University of Texas Medical Branch at Galveston, Galveston, TX, USA

Dr Whitney Yin, University of Texas Medical Branch at Galveston, Galveston, TX, USA

Dr Wlodek M. Bujalowski (UTMB), University of Texas Medical Branch at Galveston, Galveston, TX, USA

 
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Submitted on Tuesday, 5. December 2017 - 11:44 by Elżbieta Moroz Changed on Tuesday, 17. April 2018 - 11:21 by Elżbieta Moroz