|
|
| (One intermediate revision by the same user not shown) |
| Line 1: |
Line 1: |
|
| |
|
| ==S663D Stable-5-LOX== | | ==S663D Stable-5-LOX== |
| <StructureSection load='3v98' size='340' side='right' caption='[[3v98]], [[Resolution|resolution]] 2.07Å' scene=''> | | <StructureSection load='3v98' size='340' side='right'caption='[[3v98]], [[Resolution|resolution]] 2.07Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[3v98]] 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=3V98 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3V98 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[3v98]] 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=3V98 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V98 FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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]] 2.07Å</td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3o8y|3o8y]], [[3v92|3v92]], [[3v99|3v99]]</td></tr>
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3v98 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v98 OCA], [https://pdbe.org/3v98 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v98 RCSB], [https://www.ebi.ac.uk/pdbsum/3v98 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v98 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/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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3v98 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v98 OCA], [http://pdbe.org/3v98 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3v98 RCSB], [http://www.ebi.ac.uk/pdbsum/3v98 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3v98 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;">
| |
| == Publication Abstract from PubMed ==
| |
| The enzyme 5-lipoxygenase (5-LOX) initiates biosynthesis of the proinflammatory leukotriene lipid mediators and, together with 15-LOX, is also required for synthesis of the anti-inflammatory lipoxins. The catalytic activity of 5-LOX is regulated through multiple mechanisms, including Ca(2+)-targeted membrane binding and phosphorylation at specific serine residues. To investigate the consequences of phosphorylation at S663, we mutated the residue to the phosphorylation mimic Asp, providing a homogenous preparation suitable for catalytic and structural studies. The S663D enzyme exhibits robust 15-LOX activity, as determined by spectrophotometric and HPLC analyses, with only traces of 5-LOX activity remaining; synthesis of the anti-inflammatory lipoxin A(4) from arachidonic acid is also detected. The crystal structure of the S663D mutant in the absence and presence of arachidonic acid (in the context of the previously reported Stable-5-LOX) reveals substantial remodeling of helices that define the active site so that the once fully encapsulated catalytic machinery is solvent accessible. Our results suggest that phosphorylation of 5-LOX at S663 could not only down-regulate leukotriene synthesis but also stimulate lipoxin production in inflammatory cells that do not express 15-LOX, thus redirecting lipid mediator biosynthesis to the production of proresolving mediators of inflammation.-Gilbert, N. C., Rui, Z., Neau, D. B., Waight, M. T., Bartlett, S. G., Boeglin, W. E., Brash, A. R., Newcomer, M. E. Conversion of human 5-lipoxygenase to a 15-lipoxygenase by a point mutation to mimic phosphorylation at Serine-663.
| |
| | |
| Conversion of human 5-lipoxygenase to a 15-lipoxygenase by a point mutation to mimic phosphorylation at Serine-663.,Gilbert NC, Rui Z, Neau DB, Waight MT, Bartlett SG, Boeglin WE, Brash AR, Newcomer ME FASEB J. 2012 Apr 18. PMID:22516296<ref>PMID:22516296</ref>
| |
| | |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| |
| </div>
| |
| <div class="pdbe-citations 3v98" style="background-color:#fffaf0;"></div>
| |
| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Arachidonate 5-lipoxygenase]] | | [[Category: Homo sapiens]] |
| [[Category: Human]] | | [[Category: Large Structures]] |
| [[Category: Bartlett, S G]] | | [[Category: Bartlett SG]] |
| [[Category: Boeglin, W E]] | | [[Category: Boeglin WE]] |
| [[Category: Brash, A R]] | | [[Category: Brash AR]] |
| [[Category: Gilbert, N C]] | | [[Category: Gilbert NC]] |
| [[Category: Neau, D B]] | | [[Category: Neau DB]] |
| [[Category: Newcomer, M E]] | | [[Category: Newcomer ME]] |
| [[Category: Rui, Z]] | | [[Category: Rui Z]] |
| [[Category: Waight, M]] | | [[Category: Waight M]] |
| [[Category: Dioxygenase]]
| |
| [[Category: Lipoxygenase]]
| |
| [[Category: Oxidoreductase]]
| |