This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4nre

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 04:31, 5 August 2016

The structure of human 15-lipoxygenase-2 with a substrate mimic

Structural highlights

4nre is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Gene:	ALOX15B (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[LX15B_HUMAN] Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids generating a spectrum of bioactive lipid mediators. Converts arachidonic acid to 15S-hydroperoxyeicosatetraenoic acid/(15S)-HPETE. Also acts on linoleic acid to produce 13-hydroxyoctadecadienoic acid/13-HPODE. Has no detectable 8S-lipoxygenase activity but reacts with (8S)-HPETE to produce (8S,15S)-diHPETE. May regulate progression through the cell cycle and cell proliferation. May also regulate cytokine secretion by macrophages and therefore play a role in the immune response. May also regulate macrophages differentiation into proatherogenic foam cells.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

Atherosclerosis is associated with chronic inflammation occurring over decades. The enzyme 15-lipoxygenase-2 (15-LOX-2) is highly expressed in large atherosclerotic plaques, and its activity has been linked to the progression of macrophages to the lipid-laden foam cells present in atherosclerotic plaques. We report here the crystal structure of human 15-LOX-2 in complex with an inhibitor that appears to bind as a substrate mimic. 15-LOX-2 contains a long loop, composed of hydrophobic amino acids, which projects from the amino-terminal membrane-binding domain. The loop is flanked by two Ca(2+)-binding sites that confer Ca(2+)-dependent membrane binding. A comparison of the human 15-LOX-2 and 5-LOX structures reveals similarities at the active sites, as well striking differences that can be exploited for design of isoform-selective inhibitors.

The structure of human 15-lipoxygenase-2 with a substrate mimic.,Kobe MJ, Neau DB, Mitchell CE, Bartlett SG, Newcomer ME J Biol Chem. 2014 Mar 21;289(12):8562-9. doi: 10.1074/jbc.M113.543777. Epub 2014 , Feb 4. PMID:24497644^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Tang S, Bhatia B, Maldonado CJ, Yang P, Newman RA, Liu J, Chandra D, Traag J, Klein RD, Fischer SM, Chopra D, Shen J, Zhau HE, Chung LW, Tang DG. Evidence that arachidonate 15-lipoxygenase 2 is a negative cell cycle regulator in normal prostate epithelial cells. J Biol Chem. 2002 May 3;277(18):16189-201. Epub 2002 Feb 11. PMID:11839751 doi:http://dx.doi.org/10.1074/jbc.M111936200
↑ Jisaka M, Kim RB, Boeglin WE, Brash AR. Identification of amino acid determinants of the positional specificity of mouse 8S-lipoxygenase and human 15S-lipoxygenase-2. J Biol Chem. 2000 Jan 14;275(2):1287-93. PMID:10625675
↑ Bhatia B, Maldonado CJ, Tang S, Chandra D, Klein RD, Chopra D, Shappell SB, Yang P, Newman RA, Tang DG. Subcellular localization and tumor-suppressive functions of 15-lipoxygenase 2 (15-LOX2) and its splice variants. J Biol Chem. 2003 Jul 4;278(27):25091-100. Epub 2003 Apr 18. PMID:12704195 doi:http://dx.doi.org/10.1074/jbc.M301920200
↑ Jisaka M, Iwanaga C, Takahashi N, Goto T, Kawada T, Yamamoto T, Ikeda I, Nishimura K, Nagaya T, Fushiki T, Yokota K. Double dioxygenation by mouse 8S-lipoxygenase: specific formation of a potent peroxisome proliferator-activated receptor alpha agonist. Biochem Biophys Res Commun. 2005 Dec 9;338(1):136-43. Epub 2005 Aug 15. PMID:16112079 doi:http://dx.doi.org/10.1016/j.bbrc.2005.08.029
↑ Danielsson KN, Rydberg EK, Ingelsten M, Akyurek LM, Jirholt P, Ullstrom C, Forsberg GB, Boren J, Wiklund O, Hulten LM. 15-Lipoxygenase-2 expression in human macrophages induces chemokine secretion and T cell migration. Atherosclerosis. 2008 Jul;199(1):34-40. Epub 2007 Dec 11. PMID:18067895 doi:http://dx.doi.org/10.1016/j.atherosclerosis.2007.10.027
↑ Magnusson LU, Lundqvist A, Karlsson MN, Skalen K, Levin M, Wiklund O, Boren J, Hulten LM. Arachidonate 15-lipoxygenase type B knockdown leads to reduced lipid accumulation and inflammation in atherosclerosis. PLoS One. 2012;7(8):e43142. doi: 10.1371/journal.pone.0043142. Epub 2012 Aug 17. PMID:22912809 doi:http://dx.doi.org/10.1371/journal.pone.0043142
↑ Kobe MJ, Neau DB, Mitchell CE, Bartlett SG, Newcomer ME. The structure of human 15-lipoxygenase-2 with a substrate mimic. J Biol Chem. 2014 Mar 21;289(12):8562-9. doi: 10.1074/jbc.M113.543777. Epub 2014 , Feb 4. PMID:24497644 doi:http://dx.doi.org/10.1074/jbc.M113.543777

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4nre"

@@ Line 1: / Line 1: @@
 ==The structure of human 15-lipoxygenase-2 with a substrate mimic==
 <StructureSection load='4nre' size='340' side='right' caption='[[4nre]], [[Resolution|resolution]] 2.63&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C8E:(HYDROXYETHYLOXY)TRI(ETHYLOXY)OCTANE'>C8E</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ALOX15B ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4nre FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nre OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4nre RCSB], [http://www.ebi.ac.uk/pdbsum/4nre PDBsum]</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=4nre FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nre OCA], [http://pdbe.org/4nre PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4nre RCSB], [http://www.ebi.ac.uk/pdbsum/4nre PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4nre ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4nre" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4nre

From Proteopedia

Revision as of 04:31, 5 August 2016

The structure of human 15-lipoxygenase-2 with a substrate mimic

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox