Impact of heme and heme degradation products on peptides and proteins

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Heme is increasingly recognized as an essential effector molecule in biological processes where it is bound either permanently or temporarily to a wide range of proteins. These interactions are mediated by heme-binding motifs and heme-regulatory motifs. In an effort to functionally and structurally characterize these motifs with respect to their heme binding capacity and binding modes we are applying a panel of spectroscopic methods (UV/Vis, Raman, EPR, CD, NMR) using combinatorial library- and literature-derived peptides in the first approach, which subsequently is to be extended to suitable heme-protein complexes. This includes the establishment of applicable protein-based test systems allowing for investigating if protein function is altered by the heme molecule. These results will allow for a transfer of knowledge obtained on the peptide level to the protein level. On the other hand, degradation of heme is known to cause the formation of so-called heme degradation products (HDPs). These compounds will be examined for their potential to structurally and functionally influence peptides and proteins upon binding to the respective sequence stretches. This study will shed light on the essential determinants occurring in proteins that are responsible for HDP interaction and resulting conformational and functional changes. Subsequently, the information acquired from both individual approaches supplements the prerequisites for developing suitable heme and HDP detection systems. Such systems will facilitate the implementation of a diagnostic tool to monitor heme and HDP concentration in pathophysiological conditions such as cerebral vasospasm and other disorders related to an unphysiological increase of these molecules.