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@ARTICLE{Knospe:638191,
author = {Knospe, C. Vivien and Ortiz, Julio and Reiners, Jens and
Kedrov, Alexej and Gertzen, Christoph G. W. and Smits,
Sander H. J. and Schmitt, Lutz},
title = {{S}tructural insights into the substrate binding mechanism
of the class {I} dehydratase {M}ad{B}},
journal = {Communications biology},
volume = {8},
number = {1},
issn = {2399-3642},
address = {London},
publisher = {Springer Nature},
reportid = {PUBDB-2025-04009},
pages = {1032},
year = {2025},
abstract = {In the battle against antimicrobial resistance,
lantibiotics have emerged as promising new sources for
antimicrobial drugs. Their exceptional stability is due to
characteristic modifications termed (methyl-)lanthionine
rings. Genome mining efforts have identified hundreds of
lantibiotics by detecting gene operons, so-called
biosynthetic gene clusters (BGC), which encode cysteine-rich
peptides (30-50 amino acids in size) and enzymes responsible
for dehydration and cyclization, catalyzing the
post-translational ring formation. One such identified,
class I lantibiotic is maddinglicin from Clostridium
maddingley. Here, we present single particle cryo-EM
structures of the dehydratase MadB in both, its apo-state
and in complex with a leader peptide of maddinglicin,
revealing a distinct conformational change upon substrate
binding. Small-angle X-ray scattering studies elucidate the
substrate binding site for the C-terminal part of
maddinglicin. Furthermore, a substrate specificity analysis
was performed highlighting a critical stretch of amino acids
within the maddinglicin leader sequence that is crucial for
binding. Here, we provide molecular insights into the
conformational changes, principles of substrate recognition
and ligand:protein stoichiometry of a class I lantibiotic
dehydratase.},
cin = {EMBL-User},
ddc = {570},
cid = {I:(DE-H253)EMBL-User-20120814},
pnm = {6G3 - PETRA III (DESY) (POF4-6G3)},
pid = {G:(DE-HGF)POF4-6G3},
experiment = {EXP:(DE-H253)P-P12-20150101},
typ = {PUB:(DE-HGF)16},
doi = {10.1038/s42003-025-08454-5},
url = {https://bib-pubdb1.desy.de/record/638191},
}