6th7: Difference between revisions
New page: '''Unreleased structure''' The entry 6th7 is ON HOLD Authors: Koehnke, J., Sikandar, A. Description: Structure of porcine pancreatic elastase in complex with tutuilamide [[Category: Un... |
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==Structure of porcine pancreatic elastase in complex with tutuilamide== | |||
<StructureSection load='6th7' size='340' side='right'caption='[[6th7]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6th7]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TH7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TH7 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5XU:(2~{S})-2-AZANYLPROPANAL'>5XU</scene>, <scene name='pdbligand=AA4:2-AMINO-5-HYDROXYPENTANOIC+ACID'>AA4</scene>, <scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=N9K:(2~{S})-3-(4-hydroxyphenyl)-2-(methylamino)propanoic+acid'>N9K</scene>, <scene name='pdbligand=O4Q:(~{E})-4-chloranyl-3-methyl-but-3-enal'>O4Q</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=6th7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6th7 OCA], [https://pdbe.org/6th7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6th7 RCSB], [https://www.ebi.ac.uk/pdbsum/6th7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6th7 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CELA1_PIG CELA1_PIG] Acts upon elastin. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Marine cyanobacteria (blue-green algae) have been shown to possess an enormous capacity to produce structurally diverse natural products that exhibit a broad spectrum of potent biological activities, including cytotoxic, antifungal, antiparasitic, antiviral, and antibacterial activities. Using mass-spectrometry-guided fractionation together with molecular networking, cyanobacterial field collections from American Samoa and Palmyra Atoll yielded three new cyclic peptides, tutuilamides A-C. Their structures were established by spectroscopic techniques including 1D and 2D NMR, HR-MS, and chemical derivatization. Structure elucidation was facilitated by employing advanced NMR techniques including nonuniform sampling in combination with the 1,1-ADEQUATE experiment. These cyclic peptides are characterized by the presence of several unusual residues including 3-amino-6-hydroxy-2-piperidone and 2-amino-2-butenoic acid, together with a novel vinyl chloride-containing residue. Tutuilamides A-C show potent elastase inhibitory activity together with moderate potency in H-460 lung cancer cell cytotoxicity assays. The binding mode to elastase was analyzed by X-ray crystallography revealing a reversible binding mode similar to the natural product lyngbyastatin 7. The presence of an additional hydrogen bond with the amino acid backbone of the flexible side chain of tutuilamide A, compared to lyngbyastatin 7, facilitates its stabilization in the elastase binding pocket and possibly explains its enhanced inhibitory potency. | |||
Tutuilamides A-C: Vinyl-Chloride-Containing Cyclodepsipeptides from Marine Cyanobacteria with Potent Elastase Inhibitory Properties.,Keller L, Canuto KM, Liu C, Suzuki BM, Almaliti J, Sikandar A, Naman CB, Glukhov E, Luo D, Duggan BM, Luesch H, Koehnke J, O'Donoghue AJ, Gerwick WH ACS Chem Biol. 2020 Jan 28. doi: 10.1021/acschembio.9b00992. PMID:31935054<ref>PMID:31935054</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6th7" style="background-color:#fffaf0;"></div> | ||
[[Category: Koehnke | |||
==See Also== | |||
*[[Elastase 3D structures|Elastase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Sus scrofa]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Koehnke J]] | |||
[[Category: Sikandar A]] | |||
Latest revision as of 11:52, 14 July 2024
Structure of porcine pancreatic elastase in complex with tutuilamideStructure of porcine pancreatic elastase in complex with tutuilamide
Structural highlights
FunctionCELA1_PIG Acts upon elastin. Publication Abstract from PubMedMarine cyanobacteria (blue-green algae) have been shown to possess an enormous capacity to produce structurally diverse natural products that exhibit a broad spectrum of potent biological activities, including cytotoxic, antifungal, antiparasitic, antiviral, and antibacterial activities. Using mass-spectrometry-guided fractionation together with molecular networking, cyanobacterial field collections from American Samoa and Palmyra Atoll yielded three new cyclic peptides, tutuilamides A-C. Their structures were established by spectroscopic techniques including 1D and 2D NMR, HR-MS, and chemical derivatization. Structure elucidation was facilitated by employing advanced NMR techniques including nonuniform sampling in combination with the 1,1-ADEQUATE experiment. These cyclic peptides are characterized by the presence of several unusual residues including 3-amino-6-hydroxy-2-piperidone and 2-amino-2-butenoic acid, together with a novel vinyl chloride-containing residue. Tutuilamides A-C show potent elastase inhibitory activity together with moderate potency in H-460 lung cancer cell cytotoxicity assays. The binding mode to elastase was analyzed by X-ray crystallography revealing a reversible binding mode similar to the natural product lyngbyastatin 7. The presence of an additional hydrogen bond with the amino acid backbone of the flexible side chain of tutuilamide A, compared to lyngbyastatin 7, facilitates its stabilization in the elastase binding pocket and possibly explains its enhanced inhibitory potency. Tutuilamides A-C: Vinyl-Chloride-Containing Cyclodepsipeptides from Marine Cyanobacteria with Potent Elastase Inhibitory Properties.,Keller L, Canuto KM, Liu C, Suzuki BM, Almaliti J, Sikandar A, Naman CB, Glukhov E, Luo D, Duggan BM, Luesch H, Koehnke J, O'Donoghue AJ, Gerwick WH ACS Chem Biol. 2020 Jan 28. doi: 10.1021/acschembio.9b00992. PMID:31935054[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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