|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6n2w' size='340' side='right'caption='[[6n2w]], [[Resolution|resolution]] 2.71Å' scene=''> | | <StructureSection load='6n2w' size='340' side='right'caption='[[6n2w]], [[Resolution|resolution]] 2.71Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6n2w]] 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=6N2W OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6N2W FirstGlance]. <br> | + | <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='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> | + | </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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ALOX5, LOG5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Arachidonate_5-lipoxygenase Arachidonate 5-lipoxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.13.11.34 1.13.11.34] </span></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> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6n2w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n2w OCA], [http://pdbe.org/6n2w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n2w RCSB], [http://www.ebi.ac.uk/pdbsum/6n2w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n2w ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 20: |
Line 19: |
| | </div> | | </div> |
| | <div class="pdbe-citations 6n2w" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6n2w" style="background-color:#fffaf0;"></div> |
| - | | |
| - | ==See Also== | |
| - | *[[DNA polymerase 3D structures|DNA polymerase 3D structures]] | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Arachidonate 5-lipoxygenase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gilbert, N C]] | + | [[Category: Gilbert NC]] |
| - | [[Category: Neau, D B]] | + | [[Category: Neau DB]] |
| - | [[Category: Newcomer, M E]] | + | [[Category: Newcomer ME]] |
| - | [[Category: Allostery]]
| + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Lipoxygenase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
| + | |
| Structural highlights
Function
LOX5_HUMAN Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gilbert NC, Bartlett SG, Waight MT, Neau DB, Boeglin WE, Brash AR, Newcomer ME. The structure of human 5-lipoxygenase. Science. 2011 Jan 14;331(6014):217-9. PMID:21233389 doi:10.1126/science.1197203
- ↑ Gilbert NC, Gerstmeier J, Schexnaydre EE, Borner F, Garscha U, Neau DB, Werz O, Newcomer ME. Structural and mechanistic insights into 5-lipoxygenase inhibition by natural products. Nat Chem Biol. 2020 May 11. pii: 10.1038/s41589-020-0544-7. doi:, 10.1038/s41589-020-0544-7. PMID:32393899 doi:http://dx.doi.org/10.1038/s41589-020-0544-7
|
