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| | <StructureSection load='4qwt' size='340' side='right'caption='[[4qwt]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='4qwt' size='340' side='right'caption='[[4qwt]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4qwt]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Black_sea_rod Black sea rod]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QWT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QWT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4qwt]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Plexaura_homomalla Plexaura homomalla]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QWT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QWT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACD:ARACHIDONIC+ACID'>ACD</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACD:ARACHIDONIC+ACID'>ACD</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3fgi|3fgi]], [[2fnq|2fnq]], [[3fg3|3fg3]], [[3fg4|3fg4]]</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=4qwt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qwt OCA], [https://pdbe.org/4qwt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qwt RCSB], [https://www.ebi.ac.uk/pdbsum/4qwt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qwt 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_8-lipoxygenase Arachidonate 8-lipoxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.13.11.40 1.13.11.40] </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=4qwt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qwt OCA], [http://pdbe.org/4qwt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qwt RCSB], [http://www.ebi.ac.uk/pdbsum/4qwt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qwt ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AOSL_PLEHO AOSL_PLEHO]] Bifunctional enzyme which is responsible for allene oxide biosynthesis via a two-step reaction which involves conversion of arachidonic acid to a 8R-hydroperoxide intermediate followed by conversion of the hydroperoxide to allene oxide.<ref>PMID:9302294</ref> <ref>PMID:10559269</ref> | + | [https://www.uniprot.org/uniprot/AOSL_PLEHO AOSL_PLEHO] Bifunctional enzyme which is responsible for allene oxide biosynthesis via a two-step reaction which involves conversion of arachidonic acid to a 8R-hydroperoxide intermediate followed by conversion of the hydroperoxide to allene oxide.<ref>PMID:9302294</ref> <ref>PMID:10559269</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Arachidonate 8-lipoxygenase]] | |
| - | [[Category: Black sea rod]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Neau, D B]] | + | [[Category: Plexaura homomalla]] |
| - | [[Category: Newcomer, M E]] | + | [[Category: Neau DB]] |
| - | [[Category: Iron binding]] | + | [[Category: Newcomer ME]] |
| - | [[Category: Membrane-associated]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
4qwt is a 4 chain structure with sequence from Plexaura homomalla. 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
AOSL_PLEHO Bifunctional enzyme which is responsible for allene oxide biosynthesis via a two-step reaction which involves conversion of arachidonic acid to a 8R-hydroperoxide intermediate followed by conversion of the hydroperoxide to allene oxide.[1] [2]
Publication Abstract from PubMed
Lipoxygenases (LOX) play critical roles in mammalian biology in the generation of potent lipid mediators of the inflammatory response; consequently they are targets for the development of isoform-specific inhibitors. The regio- and stereo-specificity of the oxygenation of polyunsaturated fatty acids by the enzymes is understood in terms of the chemistry, but structural observation of the enzyme-substrate interactions is lacking. Although several LOX crystal structures are available, heretofore the rapid oxygenation of bound substrate has precluded capture of the enzyme-substrate complex, leaving a gap between chemical and structural insights. In this report we describe the 2.0 A resolution structure of 8R-LOX in complex with arachidonic acid (AA) obtained under anaerobic conditions. Subtle rearrangements, primarily in the side chains of three amino acids, allow binding of AA in a catalytically competent conformation. Accompanying experimental work supports a model in which both substrate tethering and cavity depth contribute to positioning the appropriate carbon at the catalytic machinery.
Crystal Structure of a Lipoxygenase in Complex with Substrate: the Arachidonic Acid Binding Site of 8R-Lipoxygenase.,Neau DB, Bender G, Boeglin WE, Bartlett SG, Brash AR, Newcomer ME J Biol Chem. 2014 Sep 17. pii: jbc.M114.599662. PMID:25231982[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Koljak R, Boutaud O, Shieh BH, Samel N, Brash AR. Identification of a naturally occurring peroxidase-lipoxygenase fusion protein. Science. 1997 Sep 26;277(5334):1994-6. PMID:9302294
- ↑ Boutaud O, Brash AR. Purification and catalytic activities of the two domains of the allene oxide synthase-lipoxygenase fusion protein of the coral Plexaura homomalla. J Biol Chem. 1999 Nov 19;274(47):33764-70. PMID:10559269
- ↑ Neau DB, Bender G, Boeglin WE, Bartlett SG, Brash AR, Newcomer ME. Crystal Structure of a Lipoxygenase in Complex with Substrate: the Arachidonic Acid Binding Site of 8R-Lipoxygenase. J Biol Chem. 2014 Sep 17. pii: jbc.M114.599662. PMID:25231982 doi:http://dx.doi.org/10.1074/jbc.M114.599662
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