Department of Structural Biology of Prokaryotic Organisms

Dr. hab. Krzysztof Brzeziński, prof. IBCH PAS

Head of Department

kbrzezinski@ibch.poznan.pl
ext. 1125

Research activity

Research area

To develop novel inhibition strategies against enzymes of pathogenic origin, a broad range of methods from the intersection of microbiology, biochemistry, biophysics including macromolecular crystallography and NMR spectroscopy, must be applied. Our studies concern:

Structural enzymology of S-adenosyl-L-homocysteine hydrolases of various origin.
Development of species-specific inhibitors targeting the enzyme dynamics.
High-throughput macromolecular crystallography.
Crystallographic studies of biologically active small molecules.
X-ray diffraction studies of non-crystalline (bio)materials.

Keywords

Macromolecular crystallography
Small molecule crystallography
Structural enzymology
Protein-ligand interactions
Antibiotic resistance
Cellular methylation
S-adenosyl-L-homocysteine hydrolase

Research Projects

Rational, structure-guided design of histone demethylase inhibitors for cancer therapy
NCN SONATA 17

Inhibition of S-adenosyl-L-homocysteine hydrolase from Pseudomonas aeruginosa by targeting the enzyme dynamics
NCN SONATA BIS 8

Selected publications

* corresponding author

Gawel, M., Malecki, P.H., Sliwiak, J., Stepniewska, M., Imiolczyk, B., Czyrko-Horczak, J., Jakubczyk, D., Marczak, L., Plonska-Brzezinska, M.E. and Brzezinski, K. A closer look at molecular mechanisms underlying inhibition of S-adenosyl-L-homocysteine hydrolase by transition metal cations. 2024. Chemical Communications60, 11504-11507. DOI: 10.1039/d4cc03143a
Hryniewicka, A., Siemiaszko, G., Breczko, J., Papathanassiou, A., Góra-Marek, K., Tarach, K.A., Brzezinski, K., Ilnicka, A., Terzyk, A., Markiewicz, K., Fernandez Delgado, O., Echegoyen, L., Plonska-Brzezinska, M.E. Three-dimensional Organization of Pyrrolo[3,2-b]pyrrole-Based Triazine Framework Using Nanostructural Spherical Carbon: Enhancing Electrochemical Performance of Materials for Supercapacitors. 2023. Scientific Reports13, 10737 DOI: 10.1038/s41598-023-37708-7
Wozniak, K. and Brzezinski, K. Biological Catalysis and Information Storage Have Relied on N-Glycosyl Derivatives of β-D-Ribofuranose since the Origins of Life. 2023. Biomolecules 13, 782. DOI: 10.3390/biom13050782
Drozdzal, P., Manszewski, T., Gilski, M., Brzezinski, K., Jaskolski, M. Right-handed Z-DNA at ultrahigh resolution: a tale of two hands and the power of the crystallographic method. (2023). Acta Crystallographica Section D79, 133-139. DOI: 10.1107/S2059798322011937
Marszalek-Zenczak, M., Satyr, A., Wojciechowski, P., Zenczak,M., Sobieszczanska, P., Brzezinski, K., Iefimenko, T., Figlerowicz, M., Zmienko, A. Analysis of Arabidopsis non-reference accessions reveals high diversity of metabolic gene clusters and discovers new candidate cluster members. (2023). Frontiers Plant Science 14, 1104303. DOI: 10.3389/fpls.2023.1104303
Malecki, P.H., Imiolczyk, B., Barciszewski, J., Czyrko-Horczak, J., Sliwiak, J., Gawel, M., Wozniak, K., Jaskolski, M. and Brzezinski, K*. Biochemical and Structural Insights into an Unusual, Alkali Metal-independent S-adenosyl-L-homocysteine Hydrolase from Synechocystis sp. PCC 6803. (2022). Acta Crystallographica Section D78, 865-882.DOI: 10.1107/S2059798322005605
Loch, J., Klonecka, A., Kądziołka, K., Bonarek, P., Barciszewski, J., Imiolczyk, B., Brzezinski, K., Jaskolski, M. Structural and biophysical studies of new L-asparaginase variants: lessons from random mutagenesis of the prototypic E. coli Ntn-amidohydrolase. (2022). Acta Crystallographica Section D78, 911-926.DOI: 10.1107/S2059798322005691
Strawa, J.W., Jakimiuk, K., Szoka Ł., Brzeziński, K., Drozdzal, P., Pałka, J.A., Tomczyk, M. New polymethoxyflavones from Hottonia palustris evoke DNA biosynthesis-inhibitory activity in an oral squamous carcinoma (SCC-25) cell line (2022). Molecules 27, 4415.DOI: 10.3390/molecules27144415
Siemiaszko, G., Hryniewicka, A., Breczko, J., Brzezinski, K., Plonska-Brzezinska, M. Carbon nano-onion induced organization of polyacrylonitrile-derived block star polymers to obtain mesoporous carbon materials. (2022). Chemical Communications, 58, 6829–6832DOI: 10.1039/d2cc01452a
Puckowska, A., Gaweł, M., Komorowska, M., Drozdzal P., Arning, A., Pawelski, D., Brzezinski, K.*, Plonska-Brzezinska, M.E.* Synthesis and Structural Characterization of Pyridine-2,6-dicarboxyamide and Furan-2,5-dicarboxyamide Derivatives. (2022). Molecules, 27, 1819.DOI: 10.3390/molecules27061819
Pawelski, D., Walewska, A., Ksiezak, S., Sredzinski, D., Radziwon, P., Moniuszko, M., Eljaszewicz, A.*, Lazny, R., Brzezinski, K.*, Plonska-Brzezinska, M.E.* Monocarbonyl Analogs of Curcumin Based on the Pseudopelletierine Scaffold: Synthesis and Anti-Inflammatory Activity. (2021). International Journal of Molecular Sciences, 22(21), 11384.DOI: 10.3390/ijms222111384
Brzezinski, K.* S-adenosyl-L-homocysteine hydrolase: a structural perspective on the enzyme with two Rossmann-fold domains. (2020). Biomolecules 10(12), 1682. DOI: 10.3390/biom10121682
Wojtulewski, S.*, Tomczyk, M., Strawa,. J.W., Gawel, M., Brzezinski, K.* A new look at two polymorphic crystal structures of dibenzoylmethane: Relationship between the Crystal Packing and the Hydrogen Atom Position revealed by Quantum Chemistry and Quantum Crystallography Methods. (2020). Acta Crystallographica Section B76, 957–966. DOI: 10.1107/S2052520620012196
Banerjee, A., Dash, S., Mohanty, M., Sahu, G., Sciortino, G., Garribba, E.*, Carvalho, M.F., Marques, F., Pessoa, J.*, Kaminsky, W., Brzezinski, K., Dinda, R.* New VIV, VIVO, VVO and VVO2 Systems: Exploring their Interconversion in Solution, Protein Interactions and Cytotoxicity. (2020). Inorganic Chemistry 59(19), 14042–14057. DOI: 10.1021/acs.inorgchem.0c01837
Regulska, E., Olejnik, P., Zubyk, H., Czyrko-Horczak, J., Chaur, M., Tomczykowa, M., Butsyk, O., Brzezinski, K., Echegoyen, L.*, Plonska-Brzezinska, M.E.* Nanostructural catalyst: metallophthalocyanine and carbon nano-onion with enhanced visible-light photocatalytic activity towards organic pollutants. (2020). RSC Advances 10, 10910-10920. DOI: 10.1039/d0ra00896f
Raczynska, J., Imiolczyk, B., Komorowska, M., Sliwiak, J., Czyrko-Horczak, J., Brzezinski, K., Jaskolski, M. Flexible loops of New Delhi metallo-β-lactamase modulate its activity towards different substrates. (2020). International Journal of Biological Macromolecules 158, 104-115. DOI: 10.1016/j.ijbiomac.2020.04.219

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