Department of Structural Biology of Eukaryotes

Dr. hab. Miłosz Ruszkowski , prof. IBCH PAS

Head of Department

mruszkowski@ibch.poznan.pl
ext. 1612

Research activity

Research area

Biological macromolecules dictate every aspect of life, but their thorough comprehension is impossible without structural information at the atomic level. Only through structures, it is possible to:
- fully understand catalytic mechanisms of enzymatic reactions;
- reveal interactions of proteins with small molecules, other proteins, DNA, and RNA;
- rationally design bioactive compounds such as drugs or herbicides.
We are particularly interested in plant proteins relevant to modern agriculture and in targets of anticancer therapies. With macromolecular crystallography and cryoelectron microscopy (Cryo-EM), complemented with a broad range of biophysical, biochemical, and bioinformatic methods, we bring new insights into the fascinating world of the molecules of life.

Keywords

biocrystallography,
Cryo-EM;
drug design;
herbicide design;
inhibitors;
metabolic pathways

Research Projects

Design and Development of Serine Hydroxymethyltransferase-2 (SHMT2) Inhibitors Blocking Tumor Growth. NCN Sonata Bis; ; PI dr hab. Milosz Ruszkowski
Search for Inhibitors of Human δ1-Pyrroline-5-Carboxylate Reductase 1 (PYCR1) as Lead Molecules for the Development of Novel Anticancer Drugs; NCN Opus; PI dr hab. Milosz Ruszkowski
The puzzling structure of Grainyhead-like human transcription factors involved in tumor growth regulation; NCN Sonatina; PI: dr. eng. Maria Rutkiewicz
Development of an efficient method of production of WRKY group IIa transcription factors from Arabidopsis thaliana for further structural studies; NCN Miniatura; PI: dr. eng. Marta Grzechowiak
Histidine Biosynthetic Pathway in Plants: Structural and Functional Studies as a Framework for the Design of Inhibitors and Activators. NCN SONATA; PI: Dr. hab. Milosz Ruszkowski
Novel L-asparaginases as potential therapeutic agents and antimicrobial targets: structural and functional studies of enzymes with dual implications for drug design. NCN OPUS; PI: Prof. Mariusz Jaskolski
Validation of PDB models of potential drug design targets for SARS-CoV-2 coronavirus. NCN COVID-19, PI: Prof. Mariusz Jaskolski
Functional and Structural Studies of Plant Serine Hydroxymethyltransferases Isoforms and Their Complexes with Small Molecules. PAS-CNR; PI: Dr. hab. Milosz Ruszkowski
Supramolecular Peptide Organic Frameworks (POFs). NCN SYMFONIA; Prof. Mariusz Jaskólski (partner).

Selected publications

Rutkiewicz, M., Nogues, I., Witek, W., Angelaccio, S., Contestabile, R., & Ruszkowski, M. (2023). Plant Physiology and Biochemistry Insights into the substrate specificity , structure , and dynamics of plant histidinol-phosphate aminotransferase ( HISN6 ). Plant Physiology and Biochemistry, 196(February), 759–773. https://doi.org/10.1016/j.plaphy.2023.02.017
Grzechowiak, M., Ruszkowska, A., Sliwiak, J., Urbanowicz, A., Jaskolski, M., & Ruszkowski, M. (2022). New aspects of DNA recognition by group II WRKY transcription factor revealed by structural and functional study of AtWRKY18 DNA binding domain. International Journal of Biological Macromolecules, 213, 589–601. https://doi.org/10.1016/j.ijbiomac.2022.05.186
Ruszkowski, M., Strugala, A., Indyka, P., Tresset, G., Figlerowicz, M., & Urbanowicz, A. (2022). Cryo-EM reconstructions of BMV-derived virus-like particles reveal assembly defects in the icosahedral lattice structure. Nanoscale, 14, 3224–3233. https://doi.org/10.1039/d1nr05650f
Tran, L. H., Urbanowicz, A., Jasiński, M., Jaskolski, M., & Ruszkowski, M. (2021). 3D Domain Swapping Dimerization of the Receiver Domain of Cytokinin Receptor CRE1 From Arabidopsis thaliana and Medicago truncatula. Frontiers in Plant Science , 12 (September). https://doi.org/10.3389/fpls.2021.756341
Ignasiak, M.,Nowicka-Bauer, K., Grzechowiak, M., Sikorski, M., Shashikadze, B., Jaskolski. M., Marciniak, B. (2021). Sensitized photo-oxidation of plant cytokinin-specific binding protein - Does the environment of the thioether group influence the oxidation reaction? From primary intermediates to stable products. Free Radical Biology and Medicine 165, 411-420. DOI: 10.1016/j.freeradbiomed.2021.02.004
Witek, W., Sliwiak, J., & Ruszkowski, M. (2021). Structural and mechanistic insights into the bifunctional HISN2 enzyme catalyzing the second and third steps of histidine biosynthesis in plants. Scientific Reports, 11(9), 9647. https://doi.org/10.1038/s41598-021-88920-2
Naskrecki, B., Dauter, Z., Jaskolski, M. (2021). A topological proof of the modified Euler characteristic based on the orbifold concept. Acta Cryst. A77, 317-326. DOI: 10.1107/S2053273321004320
Brzezinski, D., Kowiel, M., Cooper, D. R., Cymborowski, M., Grabowski, M., Wlodawer, A., Dauter, Z., Shabalin, I. G., Gilski, M., Rupp, B., Jaskolski, M., Minor, W. (2021). Covid-19.bioreproducibility.org: A web resource for SARS-CoV-2-related structural models. Protein Sci. 30, 115-124. DOI: 10.1002/pro.3959
Mao, S., Sekula, B., Ruszkowski, M., Ranganathan, S. V, Haruehanroengra, P., Wu, Y., Shen, F., & Sheng, J. (2020). Base pairing, structural and functional insights into N4-methylcytidine (m4C) and N4,N4-dimethylcytidine (m42C) modified RNA. Nucleic Acids Research, 1–14. https://doi.org/10.1093/nar/gkaa737
Kowiel, M., Brzezinski, D., Gilski, M., Jaskolski, M. (2020). Conformation-dependent restraints for polynucleotides: The sugar moiety. Nucleic Acids Res. 48, 962-973. DOI: 10.1093/nar/gkz1122
Pyrih, A., Jaskolski, M., Gzella, A. K., Lesyk, R. (2021). Synthesis, structure and evaluation of anticancer activity of 4-amino-1,3-thiazolinone/pyrazoline hybrids. J. Mol. Struct. 1224, 129059. DOI: 10.1016/j.molstruc.2020.129059
Dauter, Z., Jaskolski, M. (2020) Multiplicity-weighted Euler’s formula for symmetrically arranged space-filling polyhedra. Acta Cryst. A76, 580-583. DOI: 10.1107/S2053273320007093
Sekula, B., Ruszkowski, M., & Dauter, Z. (2020). S-adenosylmethionine synthases in plants: Structural characterization of type I and II isoenzymes from Arabidopsis thaliana and Medicago truncatula. International Journal of Biological Macromolecules, 151, 554–565. https://doi.org/10.1016/j.ijbiomac.2020.02.100
Nogués, I., Tramonti, A., Angelaccio, S., Ruszkowski, M., Sekula, B., & Contestabile, R. (2020). Structural and kinetic properties of serine hydroxymethyltransferase from the halophytic cyanobacterium Aphanothece halophytica provide a rationale for salt tolerance. International Journal of Biological Macromolecules, 159, 517–529. https://doi.org/10.1016/j.ijbiomac.2020.05.081
Grzechowiak, M., Sliwiak, J., Jaskolski, M., & Ruszkowski, M. (2020). Structural Studies of Glutamate Dehydrogenase (Isoform 1) From Arabidopsis thaliana, an Important Enzyme at the Branch-Point Between Carbon and Nitrogen Metabolism. Frontiers in Plant Science, 11(June), 1–17. https://doi.org/10.3389/fpls.2020.00754

IBCH logo