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@ARTICLE{Syllwasschy:889869,
author = {Syllwasschy, Benjamin Franz and Beck, Maximilian Steve and
Družeta, Ivona and Hopp, Marie-Thérèse and Ramoji,
Anuradha and Neugebauer, Ute and Nozinovic, Senada and
Menche, Dirk and Willbold, Dieter and Ohlenschläger, Oliver
and Kühl, Toni and Imhof, Diana},
title = {{H}igh-affinity binding and catalytic activity of
{H}is/{T}yr-based sequences: {E}xtending heme-regulatory
motifs beyond {CP}},
journal = {Biochimica et biophysica acta / General subjects},
volume = {1864},
number = {7},
issn = {0304-4165},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {FZJ-2021-00477},
pages = {129603 -},
year = {2020},
note = {Kein Post-print verfügbar},
abstract = {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.},
cin = {IBI-7},
ddc = {610},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {552 - Engineering Cell Function (POF3-552)},
pid = {G:(DE-HGF)POF3-552},
typ = {PUB:(DE-HGF)16},
pubmed = {32234408},
UT = {WOS:000536132200008},
doi = {10.1016/j.bbagen.2020.129603},
url = {https://juser.fz-juelich.de/record/889869},
}