6fph

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<StructureSection load='6fph' size='340' side='right'caption='[[6fph]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
<StructureSection load='6fph' size='340' side='right'caption='[[6fph]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6fph]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_fluorescens_liquefaciens"_flugge_1886 "bacillus fluorescens liquefaciens" flugge 1886]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FPH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FPH FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6fph]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_fluorescens Pseudomonas fluorescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FPH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FPH FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=E1W:6-chloranyl-5,7-dimethyl-4-(1~{H}-1,2,3,4-tetrazol-5-ylmethyl)-1,4-benzoxazin-3-one'>E1W</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr>
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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]] 2&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">kmo, qbsG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=294 "Bacillus fluorescens liquefaciens" Flugge 1886])</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=E1W:6-chloranyl-5,7-dimethyl-4-(1~{H}-1,2,3,4-tetrazol-5-ylmethyl)-1,4-benzoxazin-3-one'>E1W</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Kynurenine_3-monooxygenase Kynurenine 3-monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.9 1.14.13.9] </span></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=6fph FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fph OCA], [https://pdbe.org/6fph PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fph RCSB], [https://www.ebi.ac.uk/pdbsum/6fph PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fph ProSAT]</span></td></tr>
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<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=6fph FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fph OCA], [http://pdbe.org/6fph PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fph RCSB], [http://www.ebi.ac.uk/pdbsum/6fph PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fph ProSAT]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/KMO_PSEFL KMO_PSEFL]] Catalyzes the hydroxylation of L-kynurenine (L-Kyn) to form 3-hydroxy-L-kynurenine (L-3OHKyn). Probably required for the synthesis of quinolinic acid and the siderophore quinolobactin.
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[https://www.uniprot.org/uniprot/KMO_PSEFL KMO_PSEFL] Catalyzes the hydroxylation of L-kynurenine (L-Kyn) to form 3-hydroxy-L-kynurenine (L-3OHKyn). Probably required for the synthesis of quinolinic acid and the siderophore quinolobactin.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Dysregulation of the kynurenine pathway (KP) leads to imbalances in neuroactive metabolites associated with the pathogenesis of several neurodegenerative disorders, including Huntington's disease (HD). Inhibition of the enzyme kynurenine 3-monooxygenase (KMO) in the KP normalises these metabolic imbalances and ameliorates neurodegeneration and related phenotypes in several neurodegenerative disease models. KMO is thus a promising candidate drug target for these disorders, but known inhibitors are not brain permeable. Here, 19 new KMO inhibitors have been identified. One of these (1) is neuroprotective in a Drosophila HD model but is minimally brain penetrant in mice. The prodrug variant (1b) crosses the blood-brain barrier, releases 1 in the brain, thereby lowering levels of 3-hydroxykynurenine, a toxic KP metabolite linked to neurodegeneration. Prodrug 1b will advance development of targeted therapies against multiple neurodegenerative and neuroinflammatory diseases in which KP likely plays a role, including HD, Alzheimer's disease, and Parkinson's disease.
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A brain-permeable inhibitor of the neurodegenerative disease target kynurenine 3-monooxygenase prevents accumulation of neurotoxic metabolites.,Zhang S, Sakuma M, Deora GS, Levy CW, Klausing A, Breda C, Read KD, Edlin CD, Ross BP, Wright Muelas M, Day PJ, O'Hagan S, Kell DB, Schwarcz R, Leys D, Heyes DJ, Giorgini F, Scrutton NS Commun Biol. 2019 Jul 24;2:271. doi: 10.1038/s42003-019-0520-5. eCollection 2019. PMID:31372510<ref>PMID:31372510</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6fph" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
*[[Monooxygenase 3D structures|Monooxygenase 3D structures]]
*[[Monooxygenase 3D structures|Monooxygenase 3D structures]]
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== References ==
 
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<references/>
 
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Bacillus fluorescens liquefaciens flugge 1886]]
 
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[[Category: Kynurenine 3-monooxygenase]]
 
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Levy, C W]]
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[[Category: Pseudomonas fluorescens]]
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[[Category: Leys, D]]
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[[Category: Levy CW]]
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[[Category: Inhibitor]]
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[[Category: Leys D]]
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[[Category: Oxidoreductase]]
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Current revision

The crystal structure of P.fluorescens Kynurenine 3-monooxygenase (KMO) in complex with competitive inhibitor No. 1h

PDB ID 6fph

Drag the structure with the mouse to rotate

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