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| | <StructureSection load='4gvu' size='340' side='right'caption='[[4gvu]], [[Resolution|resolution]] 1.55Å' scene=''> | | <StructureSection load='4gvu' size='340' side='right'caption='[[4gvu]], [[Resolution|resolution]] 1.55Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4gvu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lyngbya Lyngbya] and [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GVU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GVU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4gvu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lyngbya Lyngbya] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GVU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GVU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6NA:HEXANOIC+ACID'>6NA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DBU:(2Z)-2-AMINOBUT-2-ENOIC+ACID'>DBU</scene>, <scene name='pdbligand=GLJ:5,5-DIHYDROXY-L-NORVALINE'>GLJ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=YNM:N-METHYL-L-TYROSINE'>YNM</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=6NA:HEXANOIC+ACID'>6NA</scene>, <scene name='pdbligand=DBU:(2Z)-2-AMINOBUT-2-ENOIC+ACID'>DBU</scene>, <scene name='pdbligand=GLJ:5,5-DIHYDROXY-L-NORVALINE'>GLJ</scene>, <scene name='pdbligand=YNM:N-METHYL-L-TYROSINE'>YNM</scene></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=4gvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gvu OCA], [https://pdbe.org/4gvu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gvu RCSB], [https://www.ebi.ac.uk/pdbsum/4gvu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gvu 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/Pancreatic_elastase Pancreatic elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.36 3.4.21.36] </span></td></tr>
| + | |
| - | <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=4gvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gvu OCA], [http://pdbe.org/4gvu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gvu RCSB], [http://www.ebi.ac.uk/pdbsum/4gvu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gvu ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CELA1_PIG CELA1_PIG]] Acts upon elastin. | + | [https://www.uniprot.org/uniprot/CELA1_PIG CELA1_PIG] Acts upon elastin. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4gvu" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4gvu" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Elastase 3D structures|Elastase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Lyngbya]] | | [[Category: Lyngbya]] |
| - | [[Category: Pancreatic elastase]] | |
| | [[Category: Sus scrofa]] | | [[Category: Sus scrofa]] |
| - | [[Category: Biggs, J S]] | + | [[Category: Biggs JS]] |
| - | [[Category: Jakoncic, J]] | + | [[Category: Jakoncic J]] |
| - | [[Category: Luesch, H]] | + | [[Category: Luesch H]] |
| - | [[Category: Ostrov, D]] | + | [[Category: Ostrov D]] |
| - | [[Category: Paul, V J]] | + | [[Category: Paul VJ]] |
| - | [[Category: Salvador, L A]] | + | [[Category: Salvador LA]] |
| - | [[Category: Taori, K]] | + | [[Category: Taori K]] |
| - | [[Category: Cyanobacteria]]
| + | |
| - | [[Category: Elastase]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Lyngbyastatin 7]]
| + | |
| Structural highlights
4gvu is a 2 chain structure with sequence from Lyngbya and Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
CELA1_PIG Acts upon elastin.
Publication Abstract from PubMed
We discovered new structural diversity to a prevalent, yet medicinally underappreciated, cyanobacterial protease inhibitor scaffold and undertook comprehensive protease profiling to reveal potent and selective elastase inhibition. Structure-activity relationship (SAR) studies and X-ray cocrystal structure analysis allowed a detailed assessment of critical and tunable structural elements. To realize the therapeutic potential of these cyclodepsipeptides, we probed the cellular effects of a novel and representative family member, symplostatin 5 (1), which attenuated the downstream cellular effects of elastase in an epithelial lung airway model system, alleviating clinical hallmarks of chronic pulmonary diseases such as cell death, cell detachment, and inflammation. This compound attenuated the effects of elastase on receptor activation, proteolytic processing of the adhesion protein ICAM-1, NF-kappaB activation, and transcriptomic changes, including the expression of pro-inflammatory cytokines IL1A, IL1B, and IL8. Compound 1 exhibited activity comparable to the clinically approved elastase inhibitor sivelestat in short-term assays and demonstrated superior sustained activity in longer-term assays.
Potent elastase inhibitors from cyanobacteria: structural basis and mechanisms mediating cytoprotective and anti-inflammatory effects in bronchial epithelial cells.,Salvador LA, Taori K, Biggs JS, Jakoncic J, Ostrov DA, Paul VJ, Luesch H J Med Chem. 2013 Feb 14;56(3):1276-90. doi: 10.1021/jm3017305. Epub 2013 Jan 28. PMID:23350733[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Salvador LA, Taori K, Biggs JS, Jakoncic J, Ostrov DA, Paul VJ, Luesch H. Potent elastase inhibitors from cyanobacteria: structural basis and mechanisms mediating cytoprotective and anti-inflammatory effects in bronchial epithelial cells. J Med Chem. 2013 Feb 14;56(3):1276-90. doi: 10.1021/jm3017305. Epub 2013 Jan 28. PMID:23350733 doi:10.1021/jm3017305
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