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Prof. Dr. Diana Imhof

University Bonn

Pharmaceutical Institute

Pharmaceutical Biochemistry and Bioanalytics

An der Immenburg 4

D-53121 Bonn

 

Telefon: 0228 73 5254
Fax: 0228 73 6829
E-Mail: dimhof [at] uni-bonn.de

 

 

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You are here: Home Areas AK Imhof Research Heme-related research

Heme-related research

Heme is one of the most intriguing molecules found in the human body. Without exception, every higher organism vitally depends on it and almost every cell can synthesize heme. The molecule fulfils numerous tasks such as oxygen transport in hemoglobin or xenobiotic detoxification in cytochromes P450. The discovery that heme is also able to function as a signalling and effector molecule has again placed it in the focus of scientific interest in the past years [1]. Heme acts as an important regulator of key biological processes such as transcription, metabolism, ion channel opening and immune regulation. In addition, it is believed to play a role in diseases such as Alzheimer’s disease, cancer, and stroke/ cerebral vasospasm [1].

 

                                                                  Heme research

 Fig. 1: Potential interactions of heme b [3].

Heme exerts its regulatory function on proteins by transient interaction (Fig. 1). In recent years our understanding of heme binding to heme-regulated proteins at distinct sites on the protein surface was expanded by a combinatorial peptide library screening [2]. Consequently, over 200 heme-peptide complexes were subjected to comprehensive spectroscopic examination within the research group FOR 1738. This approach yielded crucial information on sequence requirements, specific binding modes as well as structural properties of the formed complexes [2-10].
 

As a consequence, a general scheme for the prediction of potentially heme-regulated proteins was developed and compiled into the algorithm "SeqD-HBM", which is available to the public (will be linked here as soon as it is available) [8]. By using this algorithm, we could identify and characterize several heme-interacting proteins, as exemplified by human dipeptidyl peptidase 8 (DPP8) and the bacterial protein hemolysin C (HlyC) [2,10].

 

 

[1] Kühl, T., Imhof, D., ChemBioChem 15 (2014) 2024-2035

[2] Kühl, T., Sahoo, N., Nikolajski, M., Schlott, B., Heinemann, S. H., Imhof, D., ChemBioChem 12 (2011) 2846-2855

[3] Brewitz, H. H., Hagelueken, G., Imhof, D., Biochim Biophys Acta 1861 (2017) 683-697

[4] Kühl, T. Wißbrock, A., Goradia, N., Sahoo, N., Galler, K., Neugebauer, U., Popp, J.,Heinemann, S., Ohlenschläger, O., Imhof, D., ACS Chem. Biol. 8

     (8) (2013) 1785-1793

[5] Brewitz, H. H., Kühl, T. et al., ChemBioChem 16 (2015) 2216-2224

[6] Brewitz, H. H., Kühl, T., Goradia, N., Galler, K., Popp, J., Neugebauer, U., Ohlenschläger, O., Imhof, D., Biochim Biophys Acta 1860 (2016)

     1343-1353

[7] Wißbrock, A., Kühl, T., Silbermann, K., Becker, A. J., Ohlenschläger, O., Imhof, D., J Med     Chem 60 (2017) 373-385

[8] Wißbrock, A., Paul George, A. A., Brewitz, A. A., Kühl, T., Imhof, D., Biosci Rep (2019) doi: 10.1042/BSR20181940

[9] Kumar, A., Wißbrock, A., Goradia, N., Bellstedt, P., Ramachandran, R., Imhof, D., Ohlenschläger, O., Sci. Rep. 8 (2018) 2474

[10] Peherstorfer, S., Brewitz, H. H., Paul George, A. A., Wißbrock, A., Adam, J. M., Schmitt, L.,     Imhof, D., Biochim Biophys Acta Gen Subj 1862

       (2018) 1964-1972

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