Institute for Functional Gene Analytics (IFGA)
Unit
Department of Natural Sciences, Institute for Functional Gene Analytics (IFGA), Institute of Technology, Resource and Energy-efficient Engineering (TREE)
Location
Rheinbach
Room
E004
Address
von-Liebig-Straße 20
53359, Rheinbach
Telephone
+49 2241 865 9851Profile
Research Focus
- Analysis and rational, computer-aided development of small molecule modulators to target genetic and infection diseases
- Deciphering molecular mechanisms and allosteric coupling in molecular motors
- Understanding disease-related mutations at the atomic level and their consequences on protein structure and conformational dynamics
Methods
- X-ray crystallographic analysis of proteins and protein-ligand complexes
- High-performance computing and simulationen
- Computer-aided drug design
- Biophysical binding and activity assays
- Chemical synthesis and analytics of small molecule modulators
Teaching
- Structural Biology
- Advanced Analytical Methods 1 (Infrared Spectroscopy)
- Physikalische Chemie 2 - Struktur der Materie und Quantenchemie
- Computational Biology and Programming
- Structural Bioinformatics
Memberships
Research Projects
An analysis platform consisting of four components offers a significant expansion of biomedical analysis possibilities at Hochschule Bonn-Rhein-Sieg (H-BRS). A binding analysis device based on microscaled thermophoresis contributes an innovative approach to characterising interactions involving proteins. A multi-mode detection device for UV/Vis, fluorescence and luminescence allows, among other things, a variety of enzyme activity tests and imaging studies in new or improved form. An automated patch clamp system and a system for solid-supported membrane (SSM)-based electrophysiology for high-resolution transporter studies provide the equipment basis for expanding research into membrane transport processes and other molecular mechanisms of disease development.
Project management at the H-BRS
Prof. Dr Jörn Oliver Sass
Bio-chemical research is increasingly dependent on accurate computer modelling and analysis. This field of research is by its very nature highly interdisciplinary, as basic physical laws must be implemented algorithmically in order to make relevant contributions in life science applications. The project and the associated initiative UMMBAS bundles the strong cross-disciplinary expertise at the H-BRS in method development, visualisation and the application of computer-based procedures for deciphering material science and biochemical issues.
Project management at the H-BRS
Prof. Dr Matthias Preller
Publications
Peer-Reviewed Articles
Lin, J., Gettings, S.M., Talbi, K., Schreiber, R., Taggart, M.J., Preller, M., Kunzelmann, K., Althaus, M., Gray, M.A. (2022) Pharmacological inhibitors of the cystic fibrosis transmembrane conductance regulator exert off-target effects on epithelial cation channels. Pflugers Arch. doi: 10.1007/s00424-022-02758-9. Epub ahead of print.
Fan, L., Warnecke, A., Weder, J., Preller, M., Zeilinger, C. (2022) Triiodothyronine acts as a smart influencer of Hsp90 via a triiodothyronine binding site. Int. J. Mol. Sci., 23, 7150.
Förster, A., Brand, F., Banan, R., Hüneburg, R., Weber, C.A.M., Ewert, W., Kronenberg, J., Previti, C., Elyan, N., Beyer, U., Martens, H., Hong, B., Bräsen, J.H., Erbersdobler, A., Krauss, J.K., Stangel, M., Samii, A., Wolf, S., Preller, M., Aretz, S., Wiese, B., Hartmann, C., Weber, R.G. (2021) Rare germline variants in the E-cadherin gene CDH1 are associated with the risk of brain tumors of neuroepithelial and epithelial origin. Acta Neuropathol., 142, 191-210.
Franz, P., Ewert, W., Preller, M., Tsiavaliaris, G. (2021) Unraveling a Force-Generating Allosteric Pathway of Actomyosin Communication Associated with ADP and Pi Release. Int. J. Mol. Sci., 22, 104.
Ewert, W., Franz, P., Tsiavaliaris, G., Preller, M. (2020) Structural and computational insights into a blebbistatin-bound myosin•ADP complex with characteristics of an ADP-release conformation along the two-step myosin power stroke. Int. J. Mol. Sci., 21, 7417.
Viswanathan, M.C., Schmidt, W., Franz, P., Rynkewiecz, M.J., Newhard, C.S., Madan, A., Lehman, W., Swank, D.M., Preller, M.* and Cammarato, A.* (2020) A role for actin flexibility in thin filament-mediated contractile regulation and myopathy. Nat. Commun., 11, 2417-2432.
Osmanovic, A., Widjaja, M., Förster, A., Weder, J., Wattjes, M.P., Lange, I., Sarikidi, A., Auber, B., Raab, P., Christians, A., Preller, M., Petri, S., Weber, R.G. (2020) SPG7 mutations in amyothrophic lateral sclerosis: a genetic link to hereditary spastic paraplegia. J. Neurol., 267, 2732-2743.
Chaturvedi, A., Goparaju, R., Gupta, C., Klünemann, T., Cruz, M.M.A., Kloos, A., Goerlich, K., Schottmann, R., Struys, E.A., Ganser, A., Preller, M.* and Heuser, M.* (2019) In vivo efficacy of mutant IDH1 inhibitor HMS-101 and structural resolution of distinct binding site. Leukemia, 34, 416-426.
Shcherbakova, A., Preller, M., Taft, M.H., Pujols, J., Ventura, S., Tiemann, B., Buettner, F.F.R., Bakker, H. (2019) C-mannosylation supports folding and enhances stability of thrombospondin repeats. Elife. 8, e52978.
Ehlert, J., Kronemann, J., Zumbrägel, N., Preller, M. (2019) Lipase-catalyzed chemoselective ester hydrolysis of biomimetically coupled aryls for the synthesis of unsymmetric biphenyl esters. Molecules, 24, 4272.
Schadzek, P., Stahl, Y., Preller, M., Ngezahayo, A. (2019) Analysis of the dominant mutation N188T of human connexin46 (hCx46) using concatenation and molecular dynamics simulation. FEBS Open Bio., 9, 840-850.
Roberts, S., Seeger, M., Jiang, Y., Mishra, A., Sigmund, F, Stelzl, A., Lauri, A., Symvoulidis, P., Rolbieski, H., Preller, M., Deán-Ben, X.L., Razansky, D., Orschmann, T., Desbordes, S.C., Vetschera, P., Bach, T., Ntziachristos, V., Westmeyer, G.G. (2018). Calcium sensor for photoacoustic imaging. J. Am. Chem. Soc., 140, 2718-2721.
Chinthalapudi, K., Heissler, S., Preller, M., Sellers, J., Manstein, D.J. (2017). Mechanistic insights into the active site and allosteric communication pathways in human nonmuscle myosin-2C. Elife, 6, e32742.
Beyer, U., Brand, F., Martens, H., Weder, J., Christians, A., Elyan, N., Hentschel, B., Westphal, M., Schackert, G., Pietsch, T., Hong, B., Krauss, J.K., Samii, A., Raab, P, Das, A., Dumitru, C.A., Sandalcioglu, I.E., Hakenberg, O.W., Erbersdobler, A., Lehmann, U., Reifenberger, G., Weller, M., Reijns, M.A.M., Preller, M., Wiese, B., Hartmann, C., Weber, R.G. (2017). Rare ADAR and RNASEH2B variants and a type I interferon signature in glioma and prostate carcinoma risk and tumorigenesis. Acta Neuropathol., 134, 905-922.
Mohammadi-Ostad-Kalayeh, S., Hrupins, V., Helmsen, S., Ahlbrecht, C., Stahl, F., Scheper, T., Preller, M., Surup, F., Stadler, M., Kirschning, A., and Zeilinger, C. (2017). Development of a microarray-based assay for efficient testing of new HSP70/DnaK inhibitors. Bioorg. Med. Chem., 25, 6345-6352.
Osmanovic, A., Rangnau, I., Kosfeld, A., Abdulla, S., Janssen, C., Auber, B., Raab, P., Preller, M., Petri, S., and Weber, R.G. (2017). FIG4 variants in central European patients with amyotrophic lateral sclerosis: a whole-exome and targeted sequencing study. Eur. J. Hum. Genet., 25, 324-331.
Schadzek, P., Schlingmann, B., Schaarschmidt, F., Lindner, J., Koval, M., Heisterkamp, A., Ngezahayo, A.* and Preller, M.* (2016). Data of the molecular dynamics simulations of mutations in the human connexin46 docking interface. Data Brief, 7, 93-99.
Schadzek, P., Schlingmann, B., Schaarschmidt, F., Lindner, J., Koval, M., Heisterkamp, A., Preller, M.* and Ngezahayo, A.* (2016). The cataract related mutation N188T in human connexin46 (hCx46) revealed a critical role for residue N188 in the docking process of gap junction channels. Biochim. Biophys. Acta, 1858, 57-66.
Schuster-Gossler, K., Cordes, R., Muller, J., Geffers, I., Delany-Heiken, P., Taft, M., Preller, M. and Gossler, A. (2016). Context-Dependent Sensitivity to Mutations Disrupting the Structural Integrity of Individual EGF Repeats in the Mouse Notch Ligand DLL1. Genetics, 202, 1119-1133.
Diensthuber, R.P., Tominaga, M., Preller, M., Hartmann, F.K., Orii, H., Chizhov, I., Oiwa, K., and Tsiavaliaris, G. (2015). Kinetic mechanism of Nicotiana tabacum myosin-11 defines a new type of a processive motor. FASEB J., 29, 81-94.
Hundt, N., Preller, M., Swolski, O., Ang, A.M., Mannherz, H.G., Manstein, D.J., and Muller, M. (2014). Molecular mechanisms of disease-related human beta-actin mutations p.R183W and p.E364K. FEBS J., 281, 5279-5291.
Martin, R., Risacher, C., Barthel, A., Jäger, A., Schmidt, A.W., Richter, S., Böhl, M., Preller, M., Chinthalapudi, K., Manstein, D.J., Gutzeit, H.O., and Knölker, H.-. (2014). Silver(I)-catalyzed route to pyrroles: Synthesis of halogenated pseudilins as allosteric inhibitors for myosin ATPase and x-ray crystal structures of the protein-inhibitor complexes. Eur. J. Org. Chem., 2014, 4487-4505.
Radke, M.B., Taft, M.H., Stapel, B., Hilfiker-Kleiner, D., Preller, M., and Manstein, D.J. (2014). Small molecule-mediated refolding and activation of myosin motor function. Elife, 3, e01603.
Chaturvedi, A., Araujo Cruz, M.M., Jyotsana, N., Sharma, A., Yun, H., Gorlich, K., Wichmann, M., Schwarzer, A., Preller, M., Thol, F., Meyer, J., Haemmerle, R., Struys, E.A., Jansen, E.E., Modlich, U., Li, Z., Sly, L.M., Geffers, R., Lindner, R., Manstein, D.J., Lehmann, U., Krauter, J., Ganser, A., Heuser, M. (2013). Mutant IDH1 promotes leukemogenesis in vivo and can be specifically targeted in human AML. Blood, 122, 2877-2887.
Müller, M., Diensthuber, R.P., Chizhov, I., Claus, P., Heissler, S.M., Preller, M., Taft, M.H., and Manstein, D.J. (2013). Distinct functional interactions between actin isoforms and nonsarcomeric myosins. PLoS One, 8, e70636.
Preller, M. and Manstein, D.J. (2013). Myosin structure, allostery, and mechano-chemistry. Structure, 21, 1911-1922.
Preller, M.* and Holmes, K.C.* (2013). The myosin start-of-power stroke state and how actin binding drives the power stroke. Cytoskeleton (Hoboken), 70, 651-660.
Chinthalapudi, K., Taft, M.H., Martin, R., Heissler, S.M., Preller, M., Hartmann, F.K., Brandstaetter, H., Kendrick-Jones, J., Tsiavaliaris, G., Gutzeit, H.O., Fedorov, R., Buss, F., Knölker, H.-J., Coluccio, L. M., Manstein, D. J. (2011). Mechanism and specificity of pentachloropseudilin-mediated inhibition of myosin motor activity. J. Biol. Chem., 286, 29700-29708.
Preller, M., Bauer, S., Adamek, N., Fujita-Becker, S., Fedorov, R., Geeves, M.A., and Manstein, D.J. (2011). Structural basis for the allosteric interference of myosin function by reactive thiol region mutations G680A and G680V. J. Biol. Chem., 286, 35051-35060.
Preller, M., Chinthalapudi, K., Martin, R., Knolker, H.J., and Manstein, D.J. (2011). Inhibition of Myosin ATPase activity by halogenated pseudilins: a structure-activity study. J. Med. Chem., 54, 3675-3685.
Preller, M., Grunenberg, J., Bulychev, V.P., and Bulanin, M.O. (2011). Calculation of the structure, potential energy surface, vibrational dynamics, and electric dipole properties for the Xe:HI van der Waals complex. J. Chem. Phys., 134, 174302.
Book Chapters
Manstein, D.J. and Preller, M. (2020). Small molecule effectors of myosin function. In Advances in Experimental Medicine and Biology - Myosins, Springer Nature Ltd, ISBN: 978-3-030-38061-8.
Preller, M. and Manstein, D.J. (2017). Myosin motors: Structural aspects and functionality. In Reference Module in Life Sciences, Elsevier, ISBN: 978-0-12-809633-8.
Preller, M. and Manstein, D.J. (2012). Myosin motors: Structural aspects and functionality. In Comprehensive Biophysics, Academic Press, pp. 118-150, ISBN: 978-0-12-374920-8.
Patents
EP2727911 B1, Matthias Preller, Dietmar J. Manstein, Markus Kalesse, Novel means and methods for treating malaria and other parasitic disorders, 21.12.2016
US9499471 B2, Matthias Preller, Nina Díaz Gomez, Dietmar J. Manstein, Marcus Furch, Markus Kalesse, Biphenyl compounds for use in treating malaria and other parasitic disorders, 22.11.2016
EP2996692 A2, Michael Heuser, Anuhar Chaturvedi, Matthias Preller, Means and methods for treating cancer, 23.03.2016