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'''Unreleased structure'''


The entry 8ghc is ON HOLD
==The structure of h12-LOX in dimeric form==
<StructureSection load='8ghc' size='340' side='right'caption='[[8ghc]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ghc]] 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=8GHC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GHC FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.3&#8491;</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8ghc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ghc OCA], [https://pdbe.org/8ghc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ghc RCSB], [https://www.ebi.ac.uk/pdbsum/8ghc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ghc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LOX12_HUMAN LOX12_HUMAN] Oxygenase and 14,15-leukotriene A4 synthase activity.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human 12-lipoxygenase (12-LOX) is a key enzyme involved in platelet activation and regulation of its activity has been targeted for treatment of heparin-induced thrombocytopenia. Despite the clinical importance of 12-LOX, the exact mechanisms of how it affects platelet activation are not fully understood, and the lack of structural information has limited drug discovery efforts. In this study, we used single-particle cryo-electron microscopy to determine the high-resolution structures (1.7 A - 2.8 A) of human 12-LOX for the first time. Our results showed that 12-LOX can exist in multiple oligomeric states, from monomer to hexamer, which may impact its catalytic activity and membrane association. We also identified different conformations within a 12-LOX dimer, likely representing different time points in its catalytic cycle. Furthermore, we were able to identify small molecules bound to the 12-LOX structures. The active site of the 12-LOX tetramer is occupied by an endogenous 12-LOX inhibitor, a long-chain acyl-Coenzyme A. Additionally, we found that the 12-LOX hexamer can simultaneously bind to arachidonic acid and ML355, a selective 12-LOX inhibitor that has passed a phase I clinical trial for treating heparin-induced thrombocytopenia and has received fast-track designation by the FDA. Overall, our findings provide novel insights into the assembly of 12-LOX oligomers, its catalytic mechanism, and small molecule binding, paving the way for further drug development targeting the 12-LOX enzyme.


Authors: Black, K.A., Mobbs, J.I., Venugopal, H., Thal, D.M., Glukhova, A.
Cryo-EM structures of human arachidonate 12S-Lipoxygenase (12-LOX) bound to endogenous and exogenous inhibitors.,Mobbs JI, Black KA, Tran M, Burger WAC, Venugopal H, Holman TR, Holinstat M, Thal D, Glukhova A Blood. 2023 Jul 28:blood.2023020441. doi: 10.1182/blood.2023020441. PMID:37506345<ref>PMID:37506345</ref>


Description: The structure of h12-LOX in dimeric form form
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Mobbs, J.I]]
<div class="pdbe-citations 8ghc" style="background-color:#fffaf0;"></div>
[[Category: Venugopal, H]]
== References ==
[[Category: Thal, D.M]]
<references/>
[[Category: Glukhova, A]]
__TOC__
[[Category: Black, K.A]]
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Black KA]]
[[Category: Glukhova A]]
[[Category: Mobbs JI]]
[[Category: Thal DM]]
[[Category: Venugopal H]]
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