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Title
Structure and mechanism of an aspartimide-dependent peptide ligase in human legumain
AuthorDall, Elfriede ; Fegg, Julia C. ; Briza, Peter ; Brandstetter, Hans
Published in
Angewandte Chemie International Edition, Hoboken, 2015, Vol. 54, Issue 10, page 2015-2921
PublishedWiley, 2015
LanguageEnglish
Document typeJournal Article
ISSN1521-3773
URNurn:nbn:at:at-ubs:3-6394 Persistent Identifier (URN)
DOI10.1002/anie.201409135 
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 The work is publicly available
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Structure and mechanism of an aspartimide-dependent peptide ligase in human legumain [1.14 mb]
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Abstract (English)

Peptide ligases expand the repertoire of genetically encoded protein architectures by synthesizing new peptide bonds, energetically driven by ATP or NTPs. Here, we report the discovery of a genuine ligase activity in human legumain (AEP) which has important roles in immunity and tumor progression that were believed to be due to its established cysteine protease activity. Defying dogma, the ligase reaction is independent of the catalytic cysteine but exploits an endogenous energy reservoir that results from the conversion of a conserved aspartate to a metastable aspartimide. Legumains dual proteaseligase activities are pH- and thus localization controlled, dominating at acidic and neutral pH, respectively. Their relevance includes reversible onoff switching of cystatin inhibitors and enzyme (in)activation, and may affect the generation of three-dimensional MHC epitopes. The aspartateaspartimide (succinimide) pair represents a new paradigm of coupling endergonic reactions in ATP-scarce environments.

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