TY  - JOUR
AU  - Syllwasschy, Benjamin Franz
AU  - Beck, Maximilian Steve
AU  - Družeta, Ivona
AU  - Hopp, Marie-Thérèse
AU  - Ramoji, Anuradha
AU  - Neugebauer, Ute
AU  - Nozinovic, Senada
AU  - Menche, Dirk
AU  - Willbold, Dieter
AU  - Ohlenschläger, Oliver
AU  - Kühl, Toni
AU  - Imhof, Diana
TI  - High-affinity binding and catalytic activity of His/Tyr-based sequences: Extending heme-regulatory motifs beyond CP
JO  - Biochimica et biophysica acta / General subjects
VL  - 1864
IS  - 7
SN  - 0304-4165
CY  - Amsterdam [u.a.]
PB  - Elsevier
M1  - FZJ-2021-00477
SP  - 129603 -
PY  - 2020
N1  - Kein Post-print verfügbar
AB  - Background & motivationPeptides 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.MethodsWe 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.ResultsHeme-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.ConclusionsWe identify HXH, HXXXH, and HXXXY as potential new HRMs with functional properties. Several peptides displayed a strikingly high peroxidase-like activity.General significanceThe identification of HRMs allows to discover yet unknown heme-regulated proteins, and consequently, enhances our current understanding of pathologies involving labile heme.
LB  - PUB:(DE-HGF)16
C6  - 32234408
UR  - <Go to ISI:>//WOS:000536132200008
DO  - DOI:10.1016/j.bbagen.2020.129603
UR  - https://juser.fz-juelich.de/record/889869
ER  -