High-affinity binding and catalytic activity of His/Tyr-based sequences: Extending heme-regulatory motifs beyond CP
| Autor: | Senada Nozinovic, Dieter Willbold, Toni Kühl, Dirk Menche, Benjamin Franz Syllwasschy, Anuradha Ramoji, Diana Imhof, Ivona Družeta, Maximilian Steve Beck, Ute Neugebauer, Marie-Thérèse Hopp, Oliver Ohlenschläger |
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| Rok vydání: | 2020 |
| Předmět: |
Hemeproteins
0301 basic medicine chemistry.chemical_classification Amyloid beta-Peptides Magnetic Resonance Spectroscopy Dipeptide Heme binding High affinity binding Chemistry Stereochemistry Biophysics Heme Biochemistry Amino acid Catalysis 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Peroxidases Peptide synthesis Molecular Biology Two-dimensional nuclear magnetic resonance spectroscopy 030217 neurology & neurosurgery |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - General Subjects. 1864:129603 |
| ISSN: | 0304-4165 |
| DOI: | 10.1016/j.bbagen.2020.129603 |
| Popis: | Background & motivation Peptides and proteins can interact with heme through His, Tyr, or Cys in heme-regulatory motifs (HRMs). The Cys-Pro dipeptide is a well investigated HRM, but for His and Tyr such a distinct motif is currently unknown. In addition, many heme-peptide complexes, such as heme-amyloid β, can display a peroxidase-like activity, albeit there is little understanding of how the local primary and secondary coordination environment influences catalytic activity. We thus systematically evaluated a series of His- and Tyr-based peptides to identify sequence features for high-affinity heme binding and their impact on the catalytic activity of heme. Methods We employed solid-phase peptide synthesis to produce 58 nonapeptides, which were investigated by UV/vis, resonance Raman, and 2D NMR spectroscopy. A chromogenic assay was used to determine the catalytic activity of the heme-peptide complexes. Results Heme-binding affinity and binding mode were found to be dependent on the coordinating amino acid and spacer length between multiple potential coordination sites in a motif. In particular, HXH and HXXXH motifs showed strong heme binding. Analysis of the peroxidase-like activity revealed that some of these peptides and also HXXXY motifs enhance the catalytic activity of heme significantly. Conclusions We identify HXH, HXXXH, and HXXXY as potential new HRMs with functional properties. Several peptides displayed a strikingly high peroxidase-like activity. General significance The identification of HRMs allows to discover yet unknown heme-regulated proteins, and consequently, enhances our current understanding of pathologies involving labile heme. |
| Databáze: | OpenAIRE |
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