6lke

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(New page: '''Unreleased structure''' The entry 6lke is ON HOLD Authors: Description: Category: Unreleased Structures)
Current revision (11:02, 22 November 2023) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 6lke is ON HOLD
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==in meso full-length rat KMO in complex with an inhibitor identified via DNA-encoded chemical library screening==
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<StructureSection load='6lke' size='340' side='right'caption='[[6lke]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[6lke]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LKE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LKE FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EGU:4-chloranyl-2-[[5-chloranyl-2-(5-methoxy-1,3-dihydroisoindol-2-yl)-1,3-thiazol-4-yl]carbonyl-methyl-amino]-5-fluoranyl-benzoic+acid'>EGU</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6lke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lke OCA], [https://pdbe.org/6lke PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lke RCSB], [https://www.ebi.ac.uk/pdbsum/6lke PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lke ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/KMO_RAT KMO_RAT] Catalyzes the hydroxylation of L-kynurenine (L-Kyn) to form 3-hydroxy-L-kynurenine (L-3OHKyn). Required for synthesis of quinolinic acid, a neurotoxic NMDA receptor antagonist and potential endogenous inhibitor of NMDA receptor signaling in axonal targeting, synaptogenesis and apoptosis during brain development. Quinolinic acid may also affect NMDA receptor signaling in pancreatic beta cells, osteoblasts, myocardial cells, and the gastrointestinal tract.[HAMAP-Rule:MF_03018]<ref>PMID:26752518</ref> <ref>PMID:28398044</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The structural mechanisms of single-pass transmembrane enzymes remain elusive. Kynurenine 3-monooxygenase (KMO) is a mitochondrial protein involved in the eukaryotic tryptophan catabolic pathway and is linked to various diseases. Here, we report the mammalian full-length structure of KMO in its membrane-embedded form, complexed with compound 3 (identified internally) and compound 4 (identified via DNA-encoded chemical library screening) at 3.0 A resolution. Despite predictions suggesting that KMO has two transmembrane domains, we show that KMO is actually a single-pass transmembrane protein, with the other transmembrane domain lying laterally along the membrane, where it forms part of the ligand-binding pocket. Further exploration of compound 3 led to identification of the brain-penetrant compound, 5. We show that KMO is dimeric, and that mutations at the dimeric interface abolish its activity. These results will provide insight for the drug discovery of additional blood-brain-barrier molecules, and help illuminate the complex biology behind single-pass transmembrane enzymes.
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Authors:
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Full-length in meso structure and mechanism of rat kynurenine 3-monooxygenase inhibition.,Mimasu S, Yamagishi H, Kubo S, Kiyohara M, Matsuda T, Yahata T, Thomson HA, Hupp CD, Liu J, Okuda T, Kakefuda K Commun Biol. 2021 Feb 4;4(1):159. doi: 10.1038/s42003-021-01666-5. PMID:33542467<ref>PMID:33542467</ref>
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Description:
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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<div class="pdbe-citations 6lke" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Monooxygenase 3D structures|Monooxygenase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
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[[Category: Rattus norvegicus]]
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[[Category: Hupp DC]]
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[[Category: Kakefuda K]]
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[[Category: Kiyohara M]]
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[[Category: Liu J]]
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[[Category: Mimasu S]]
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[[Category: Okuda T]]
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[[Category: Yamagishi H]]

Current revision

in meso full-length rat KMO in complex with an inhibitor identified via DNA-encoded chemical library screening

PDB ID 6lke

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