Structural highlights
4n6o is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , |
| NonStd Res: | |
| Related: | 4n6l, 4n6m, 4n6n |
| Activity: | Legumain, with EC number 3.4.22.34 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[LGMN_HUMAN] Has a strict specificity for hydrolysis of asparaginyl bonds. Can also cleave aspartyl bonds slowly, especially under acidic conditions. May be involved in the processing of proteins for MHC class II antigen presentation in the lysosomal/endosomal system. [CYTM_HUMAN] Shows moderate inhibition of cathepsin B but is not active against cathepsin C.
Publication Abstract from PubMed
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. Legumain's dual protease-ligase activities are pH- and thus localization controlled, dominating at acidic and neutral pH, respectively. Their relevance includes reversible on-off switching of cystatin inhibitors and enzyme (in)activation, and may affect the generation of three-dimensional MHC epitopes. The aspartate-aspartimide (succinimide) pair represents a new paradigm of coupling endergonic reactions in ATP-scarce environments.
Structure and Mechanism of an Aspartimide-Dependent Peptide Ligase in Human Legumain.,Dall E, Fegg JC, Briza P, Brandstetter H Angew Chem Int Ed Engl. 2015 Jan 28. doi: 10.1002/anie.201409135. PMID:25630877[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dall E, Fegg JC, Briza P, Brandstetter H. Structure and Mechanism of an Aspartimide-Dependent Peptide Ligase in Human Legumain. Angew Chem Int Ed Engl. 2015 Jan 28. doi: 10.1002/anie.201409135. PMID:25630877 doi:http://dx.doi.org/10.1002/anie.201409135
