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@ARTICLE{Dall:894963,
author = {Dall, Elfriede and Stanojlovic, Vesna and Demir, Fatih and
Briza, Peter and Dahms, Sven O. and Huesgen, Pitter F. and
Cabrele, Chiara and Brandstetter, Hans},
title = {{T}he {P}eptide {L}igase {A}ctivity of {H}uman {L}egumain
{D}epends on {F}old {S}tabilization and {B}alanced
{S}ubstrate {A}ffinities},
journal = {ACS catalysis},
volume = {11},
number = {19},
issn = {2155-5435},
address = {Washington, DC},
publisher = {ACS},
reportid = {FZJ-2021-03503},
pages = {11885 - 11896},
year = {2021},
abstract = {Protein modification by enzymatic breaking and forming of
peptide bonds significantly expands the repertoire of
genetically encoded protein sequences. The dual
protease-ligase legumain exerts the two opposing activities
within a single protein scaffold. Primarily localized to the
endolysosomal system, legumain represents a key enzyme in
the generation of antigenic peptides for subsequent
presentation on the MHCII complex. Here we show that human
legumain catalyzes the ligation and cyclization of linear
peptides at near-neutral pH conditions, where legumain is
intrinsically unstable. Conformational stabilization
significantly enhanced legumain’s ligase activity, which
further benefited from engineering the prime substrate
recognition sites for improved affinity. Additionally, we
provide evidence that specific legumain activation states
allow for differential regulation of its activities.
Together these results set the basis for engineering
legumain proteases and ligases with applications in
biotechnology and drug development.},
cin = {ZEA-3},
ddc = {540},
cid = {I:(DE-Juel1)ZEA-3-20090406},
pnm = {2171 - Biological and environmental resources for
sustainable use (POF4-217) / ProPlantStress - Proteolytic
processing in plant stress signal transduction and responses
to abiotic stress and pathogen attack (639905)},
pid = {G:(DE-HGF)POF4-2171 / G:(EU-Grant)639905},
typ = {PUB:(DE-HGF)16},
pubmed = {34621593},
UT = {WOS:000704700800008},
doi = {10.1021/acscatal.1c02057},
url = {https://juser.fz-juelich.de/record/894963},
}