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| | ==Crystal structure of prolegumain== | | ==Crystal structure of prolegumain== |
| - | <StructureSection load='4fgu' size='340' side='right' caption='[[4fgu]], [[Resolution|resolution]] 3.90Å' scene=''> | + | <StructureSection load='4fgu' size='340' side='right'caption='[[4fgu]], [[Resolution|resolution]] 3.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4fgu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FGU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FGU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4fgu]] 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=4FGU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FGU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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]] 3.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4aw9|4aw9]], [[4awa|4awa]], [[4awb|4awb]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LGMN, PRSC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4fgu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fgu OCA], [https://pdbe.org/4fgu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fgu RCSB], [https://www.ebi.ac.uk/pdbsum/4fgu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fgu 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=4fgu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fgu OCA], [http://pdbe.org/4fgu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4fgu RCSB], [http://www.ebi.ac.uk/pdbsum/4fgu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4fgu 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. | + | [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: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Legumain]] | + | [[Category: Large Structures]] |
| - | [[Category: Brandstetter, H]] | + | [[Category: Brandstetter H]] |
| - | [[Category: Dall, E]] | + | [[Category: Dall E]] |
| - | [[Category: Aep]]
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| - | [[Category: Antigen processing]]
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| - | [[Category: Asparaginyl endopeptidase]]
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| - | [[Category: Cancer]]
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| - | [[Category: Cysteine protease]]
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| - | [[Category: Hydrolase]]
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| - | [[Category: Lysosomal]]
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| - | [[Category: Mhcii]]
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| - | [[Category: Proenzyme]]
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| - | [[Category: Substrate specificity]]
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| Structural highlights
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
The cysteine protease legumain plays important functions in immunity and cancer at different cellular locations, some of which appeared conflicting with its proteolytic activity and stability. Here, we report crystal structures of legumain in the zymogenic and fully activated form in complex with different substrate analogs. We show that the eponymous asparagine-specific endopeptidase activity is electrostatically generated by pH shift. Completely unexpectedly, the structure points toward a hidden carboxypeptidase activity that develops upon proteolytic activation with the release of an activation peptide. These activation routes reconcile the enigmatic pH stability of legumain, e.g., lysosomal, nuclear, and extracellular activities with relevance in immunology and cancer. Substrate access and turnover is controlled by selective protonation of the S1 pocket (KM) and the catalytic nucleophile (kcat), respectively. The multibranched and context-dependent activation process of legumain illustrates how proteases can act not only as signal transducers but as decision makers.
Mechanistic and structural studies on legumain explain its zymogenicity, distinct activation pathways, and regulation.,Dall E, Brandstetter H Proc Natl Acad Sci U S A. 2013 Jun 17. PMID:23776206[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dall E, Brandstetter H. Mechanistic and structural studies on legumain explain its zymogenicity, distinct activation pathways, and regulation. Proc Natl Acad Sci U S A. 2013 Jun 17. PMID:23776206 doi:10.1073/pnas.1300686110
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