Dr. Jacek Kozuch
Department of Physics
Institute of Experimental Physics
Experimental Molecular Biophysics
Project Director
Room 1.1.35
14195 Berlin
Electrostatic Effects in Biological Processes
I aim at understanding how electrostatic interactions sculpt structural motifs in biological macromolecules and give rise to their unrivalled functionalities. In particular, I am interested in such structures found in enzymatic active sites, ion/proton channel pores as well as complex assemblies within biological membranes.
I explore this question with a particular focus on the mechanisms of evolution towards antimicrobial resistances, which present a major global health issue of today’s world. As such, I have studied the evolution of electrostatic catalysis in antibiotic resistance against β-lactam antibiotics previously. Now, I am extending this concept to the interplay between electrostatic and protonation effects, for instance, in the proton conductance through viral proton channels as part of the Collaborative Research Center 1078 (https://www.sfb1078.de/). Towards this goal I use a multidisciplinary experimental and theoretical approach centered around advanced vibrational spectroscopic approaches.
Peer-Reviewed Publications
31. R. R. Paschke, S. Mohr, S. Lange, A. Lange, J. Kozuch, In situ spectroscopic detection of large-scale reorientations of transmembrane helices during influenza A M2 channel opening, Angew. Chem. Int. Ed., 2023, accepted
https://doi.org/10.1002/anie.202309069
30. J. Kozuch, K. Ataka, J. Heberle, Surface-enhanced infrared absorption spectroscopy, Nat. Rev. Methods Primers, 2023, 3, 70-20954.
https://doi.org/10.1038/s43586-023-00253-8
29. Z. Ji, J. Kozuch, I. I. Mathews, C. S. Diercks, Y. Shamsudin, M. A. Schulz, S. G. Boxer, Protein electric fields enable faster and longer-lasting covalent inhibition of beta-lactamases, J. Am. Chem. Soc., 2022, 144, 20947-20954.
https://doi.org/10.1021/jacs.2c09876
28. T. Utesch, J. K. Staffa, S. Katz, G. Yao, J. Kozuch, P. Hildebrandt, Potential distribution across model membranes, J. Phys. Chem. B, 2022. 126, 7664-7675.
https://doi.org/10.1021/acs.jpcb.2c05372
27. C. Zheng, Y. Mao, J. Kozuch, A. Atsango, Z. Ji, T. Markland, S. G. Boxer, Electric field orientations in solution and enzyme active site revealed by a two-dimensional vibrational probe, Nat. Chem., 2022, 14, 891-897.
https://doi.org/10.1038/s41557-022-00937-w
26. J. B. Weaver, J. Kozuch, J. M. Kirsh, S. G. Boxer, Nitrile IR intensities characterize electric fields and hydrogen bonding in protic, aprotic, and protein environments, J. Am. Chem. Soc., 2022, 144, 7562–7567.
https://doi.org/10.1021/jacs.2c00675
25. M. La Greca, J. L. Chen, L. Schubert, J. Kozuch, T. Berneiser, U. Terpitz, J. Heberle, R. Schlesinger, The Photoreaction of the Proton-Pumping Rhodopsin 1 From the Maize Pathogenic Basidiomycete Ustilago maydis, Front. Mol. Biosci., 2022, 9, 829660.
https://doi.org/10.3389/fmolb.2022.826990
24. S. H. Schneider, J. Kozuch, S. G. Boxer, The interplay of electrostatics and chemical positioning in the evolution of antibiotic resistance in TEM beta-lactamases, ACS Cent. Sci., 2021, 7, 1996-2008.
https://doi.org/10.1101/2021.05.27.446023
23. A. Kraskov, J. Von Sass, A. D. Nguyen, T. O. Hoang, D. Buhrke, S. Katz, N. Michael, J. Kozuch, I. Zebger, F. Siebert, P. Scheerer, M. A. Mroginski, N. Budisa, P. Hildebrandt, Local Electric Field Changes during the Photoconversion of the Bathy Phytochrome Agp2, Biochemistry, 2021, 60, 2967-2977.
https://doi.org/10.1021/acs.biochem.1c00426
22. J. Kozuch, S. H. Schneider, C. Zheng, Z. Ji, R. T. Bradshaw, S. G. Boxer, Testing the limitations of MD-based local electric fields using the vibrational Stark effect in solution: pencillin G as a test case, J. Phys. Chem. B, 2021, 125, 4415-4427.
https://doi.org/10.1021/acs.jpcb.1c00578
21. F. Baserga, J. Drageli, J. Kozuch, H. Mohrmann, E.-W. Knapp. S. T. Stripp, J. Heberle, Quantification of local electric field changes in the active site of cytochrome c oxidase by FTIR spectroelectrochemical titrations, Front. Chem., 2021, 9, 669452.
https://doi.org/10.3389/fchem.2021.669452
20. J. Kozuch, S. H. Schneider, S. G. Boxer Biosynthetic incorporation of site-specific isotopes in β-lactam antibiotics enables biophysical studies, ACS Chem. Bio., 2020, 15, 1148-1153.
https://doi.org/10.1021/acschembio.9b01054
19. U. Szczepaniak, S. H. Schneider, R. Horvath, J. Kozuch, M. Geiser Vibrational Stark spectroscopy of fluorobenzene using quantum cascade laser dual frequency combs, Appl. Spec., 2020, 74, 347-356.
https://doi.org/10.1177/0003702819888503
18. A. de Miguel Catalina, E. Forbrig, J. Kozuch, C. Nehls, L. Paulowski, T. Gutsmann, P. Hildebrandt, M. A. Mroginski The C-terminal VPRTES tail of LL-37 influences the mode of attachment to a lipid bilayer and antimicrobial activity, Biochemistry, 2019, 58, 2447-2464.
https://doi.org/10.1021/acs.biochem.8b01297
17. M. Caterino, M. Herrmann, A. Merlino, C. Ricciardi, D. Montesarchio, M. A. Mroginski, D. Musumeci, F. Ruffo, L. Paduano, P. Hildebrandt, J. Kozuch, A. Vergara On the pH-modulated Ru-based pro-drug activation mechanism, Inorg. Chem., 2018, 58, 1216-1223.
https://doi.org/10.1021/acs.inorgchem.8b02667
16. H. Biava, T. Schreiber, S. Katz, J.-S. Völler, M. Stolarski, C. Schulz, N. Michael, N. Budisa, J. Kozuch, T. Utesch, P. Hildebrandt Long-range modulations of the electric fields in proteins, J. Phys. Chem. B, 2018, 122, 8330-8342.
https://doi.org/10.1021/acs.jpcb.8b03870
15. T. G. G. A. Harris, N. Heidary, J. Kozuch, S. Frielingsdorf, O. Lenz, M. A. Mroginski, P. Hildebrandt, I. Zebger, A. Fischer, In situ spectroelectrochemical studies into the formation and stability of robust diazoniumderived interfaces on gold electrodes for the immobilization of an oxygen-tolerant hydrogenase, ACS Appl. Mater. Interfaces, 2018, 10, 23380-23391.
https://doi.org/10.1021/acsami.8b02273
14. O. Gutierrez-Sanz, E. Forbrig, A. P. Batista, M. I. Pereira, J. Salewski, M. A. Mroginski, R. Götz, A. L. De Lacey, J. Kozuch, I. Zebger, Catalytic activity and proton translocation of reconstituted respiratory complex I monitored by surface-enhanced infrared absorption spectroscopy, Langmuir, 2018, 34, 57023-5711.
https://doi.org/10.1021/acs.langmuir.7b04057
13. P. Kielb, M. Horch, P. Wrzolek, R. Götz, H. K. Ly, J. Kozuch, M. Schwalbe, I. Weidinger, Hydrogen Evolution by cobalt hangman porphyrins under operating conditions studied by vibrational spectro-electrochemistry, Catal. Sci. Technol., 2018, 8, 1849-1857.
https://doi.org/10.1039/C7CY02253K
12. E. Forbrig, J. K. Staffa, J. Salewski, M. A. Mroginski, P. Hildebrandt, J. Kozuch, Monitoring the orientational changes of alamethicin during incorporation in bilayer lipid membranes, Langmuir, 2018, 34, 2373-2385.
https://doi.org/10.1021/acs.langmuir.7b04265
11. J. K. Staffa, L. Lorenz, M. Stolarski, D. H. Murgida, I. Zebger, T. Utesch, J. Kozuch, P. Hildebrandt, Determination of the local electric field at Au/SAM interfaces using the vibrational Stark effect, J. Phys. Chem. C, 2017, 121, 22274-22285.
https://doi.org/10.1021/acs.jpcc.7b08434
10. P. Kielb, T. Utesch, J. Kozuch, J.-H. Jeoung, H. Dobbek, M. A. Mroginski, P. Hildebrandt, I. Weidinger, Switchable redox chemistry of the hexameric tyrosine-coordinated heme protein, J. Phys. Chem. B, 2017, 121, 3955-3964.
https://doi.org/10.1021/acs.jpcb.7b01286
9. S. Wiebalck, J. Kozuch, C. C. Tzschucke, L. J. C. Jeuken, P. Hildebrandt, Monitoring the transmembrane proton gradient generated by cytochrome bo3 in tethered bilayer lipid membranes using SEIRA spectroscopy, J. Phys. Chem. B, 2016, 120, 22492256.
https://doi.org/10.1021/acs.jpcb.6b01435
8. H. K. Ly, P. Wrzolek, N. Heidary, R. Götz, M. Horch, J. Kozuch, M. Schwalbe, I. Weidinger, 2nd coordination sphere controlled electron transfer of iron hangman complexes on rlectrodes probed by surface-enhanced vibrational spectroscopy, Chem. Sci., 2015, 6, 6999-7007.
https://doi.org/10.1039/C5SC02560E
7. J. Kozuch, N. Petrusch, D. Gkogkou, U. Gernert, I. M. Weidinger, Calculating average surface-enhancement factors of randomly nanostructured electrodes by a combination of SERS and impedance Spectroscopy, Phys. Chem. Chem. Phys., 2015, 17, 21220-21225.
https://doi.org/10.1039/C4CP05015K
6. J. Kozuch, C. Weichbrodt, D. Millo, K. Giller, S. Becker, P. Hildebrandt, C. Steinem, Voltage-dependent structural changes of the membrane-bound anion channel hVDAC1 probed by SEIRA and electrochemical impedance spectroscopy, Phys. Chem. Chem. Phys., 2014, 16, 9546-9555.
https://doi.org/10.1039/C4CP00167B
5. X. X. Han, C. Köhler, J. Kozuch, U. Kuhlmann, L. Paasche, A. Sivanesan, I. M. Weidinger, P. Hildebrandt, Potential-Dependent surface-enhanced resonance Raman spectroscopy at nanostructured TiO2: a case study on cytochrome b5, Small, 2013, 9, 4175-4181.
https://doi.org/10.1002/smll.201301070
4. J. Kozuch, I. von der Hocht, F. Hilbers, H. Michel, I. M. Weidinger, Resonance Raman Characterization of the ammonia-generated intermediate of cytochrome c oxidase from Paracoccus denitrificans. Biochemistry, 2013, 52, 6197-6202.
https://doi.org/10.1021/bi400535m
3. J. Kozuch, C. Steinem, P. Hildebrandt, D. Millo, Combined electrochemistry and surface-enhanced infrared absorption spectroscopy of gramicidin A incorporated into tethered bilayer lipid membranes. Angew. Chem. Int. Ed., 2012, 51, 8114-8117.
https://doi.org/10.1002/anie.201203214
2. A. Sivanesan, J. Kozuch, H. K. Ly, G. Kalaivani, A. Fischer, I. M. Weidinger, Tailored silica coated Ag nanoparticles for non-invasive surface enhanced Raman spectroscopy of biomolecular targets, RSC Adv., 2012, 2, 805-808.
https://doi.org/10.1039/C1RA00781E
1. A. Sivanesan, H. K. Ly, J. Kozuch, M. Sezer, U. Kuhlmann, A. Fischer, I. M. Weidinger, Functionalized Ag nanoparticles with tunable optical properties for selective protein analysis, Chem. Commun., 2011, 47, 3553-3555.
https://doi.org/10.1039/C0CC05058J