6n2w: Difference between revisions
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The | ==The structure of Stable-5-Lipoxygenase bound to NDGA== | ||
<StructureSection load='6n2w' size='340' side='right'caption='[[6n2w]], [[Resolution|resolution]] 2.71Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6n2w]] 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=6N2W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6N2W 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]] 2.71Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=30Z:4-[(2R,3S)-3-[(3,4-DIHYDROXYPHENYL)METHYL]-2-METHYLBUTYL]BENZENE-1,2-DIOL'>30Z</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</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=6n2w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n2w OCA], [https://pdbe.org/6n2w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6n2w RCSB], [https://www.ebi.ac.uk/pdbsum/6n2w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6n2w ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/LOX5_HUMAN LOX5_HUMAN] Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.<ref>PMID:21233389</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Leukotrienes (LT) are lipid mediators of the inflammatory response that are linked to asthma and atherosclerosis. LT biosynthesis is initiated by 5-lipoxygenase (5-LOX) with the assistance of the substrate-binding 5-LOX-activating protein at the nuclear membrane. Here, we contrast the structural and functional consequences of the binding of two natural product inhibitors of 5-LOX. The redox-type inhibitor nordihydroguaiaretic acid (NDGA) is lodged in the 5-LOX active site, now fully exposed by disordering of the helix that caps it in the apo-enzyme. In contrast, the allosteric inhibitor 3-acetyl-11-keto-beta-boswellic acid (AKBA) from frankincense wedges between the membrane-binding and catalytic domains of 5-LOX, some 30 A from the catalytic iron. While enzyme inhibition by NDGA is robust, AKBA promotes a shift in the regiospecificity, evident in human embryonic kidney 293 cells and in primary immune cells expressing 5-LOX. Our results suggest a new approach to isoform-specific 5-LOX inhibitor development through exploitation of an allosteric site in 5-LOX. | |||
Structural and mechanistic insights into 5-lipoxygenase inhibition by natural products.,Gilbert NC, Gerstmeier J, Schexnaydre EE, Borner F, Garscha U, Neau DB, Werz O, Newcomer ME Nat Chem Biol. 2020 May 11. pii: 10.1038/s41589-020-0544-7. doi:, 10.1038/s41589-020-0544-7. PMID:32393899<ref>PMID:32393899</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Gilbert | <div class="pdbe-citations 6n2w" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Gilbert NC]] | |||
[[Category: Neau DB]] | |||
[[Category: Newcomer ME]] | |||
Latest revision as of 06:44, 11 October 2023
The structure of Stable-5-Lipoxygenase bound to NDGA
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