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| ==Crystal structure of oxidized legumain in complex with cystatin E/M== | | ==Crystal structure of oxidized legumain in complex with cystatin E/M== |
- | <StructureSection load='4n6n' size='340' side='right' caption='[[4n6n]], [[Resolution|resolution]] 1.87Å' scene=''> | + | <StructureSection load='4n6n' size='340' side='right'caption='[[4n6n]], [[Resolution|resolution]] 1.87Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[4n6n]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N6N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4N6N FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4n6n]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N6N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4N6N FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.87Å</td></tr> |
- | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SCH:S-METHYL-THIO-CYSTEINE'>SCH</scene>, <scene name='pdbligand=SNN:L-3-AMINOSUCCINIMIDE'>SNN</scene></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SCH:S-METHYL-THIO-CYSTEINE'>SCH</scene>, <scene name='pdbligand=SNN:L-3-AMINOSUCCINIMIDE'>SNN</scene></td></tr> |
- | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4n6l|4n6l]], [[4n6m|4n6m]], [[4n6o|4n6o]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4n6n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n6n OCA], [https://pdbe.org/4n6n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4n6n RCSB], [https://www.ebi.ac.uk/pdbsum/4n6n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4n6n ProSAT]</span></td></tr> |
- | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Legumain Legumain], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.34 3.4.22.34] </span></td></tr>
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- | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4n6n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n6n OCA], [http://pdbe.org/4n6n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4n6n RCSB], [http://www.ebi.ac.uk/pdbsum/4n6n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4n6n ProSAT]</span></td></tr> | + | |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[http://www.uniprot.org/uniprot/LGMN_HUMAN 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. [[http://www.uniprot.org/uniprot/CYTM_HUMAN CYTM_HUMAN]] Shows moderate inhibition of cathepsin B but is not active against cathepsin C. | + | [https://www.uniprot.org/uniprot/LGMN_HUMAN 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. |
| <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
- | [[Category: Legumain]] | + | [[Category: Homo sapiens]] |
- | [[Category: Brandstetter, H]] | + | [[Category: Large Structures]] |
- | [[Category: Dall, E]] | + | [[Category: Brandstetter H]] |
- | [[Category: Asparaginyl endopeptidase]] | + | [[Category: Dall E]] |
- | [[Category: Cancer]]
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- | [[Category: Cathepsin]]
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- | [[Category: Complex]]
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- | [[Category: Cysteine protease]]
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- | [[Category: Hydrolase-hydrolase inhibitor complex]]
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- | [[Category: Inhibitor]]
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- | [[Category: Papain]]
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- | [[Category: Reactive center loop]]
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| Structural highlights
4n6n is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| Method: | X-ray diffraction, Resolution 1.87Å |
Ligands: | , , , , |
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.
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
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