6fp1
From Proteopedia
(Difference between revisions)
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<StructureSection load='6fp1' size='340' side='right'caption='[[6fp1]], [[Resolution|resolution]] 1.97Å' scene=''> | <StructureSection load='6fp1' size='340' side='right'caption='[[6fp1]], [[Resolution|resolution]] 1.97Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6fp1]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FP1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FP1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6fp1]] 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=6FP1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FP1 FirstGlance]. <br> |
</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=E0Q:2-(6-chloranyl-5,7-dimethyl-3-oxidanylidene-1,4-benzoxazin-4-yl)ethanoic+acid'>E0Q</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | </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=E0Q:2-(6-chloranyl-5,7-dimethyl-3-oxidanylidene-1,4-benzoxazin-4-yl)ethanoic+acid'>E0Q</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | ||
| + | <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> | ||
<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> | <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> | ||
<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=6fp1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fp1 OCA], [http://pdbe.org/6fp1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fp1 RCSB], [http://www.ebi.ac.uk/pdbsum/6fp1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fp1 ProSAT]</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=6fp1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fp1 OCA], [http://pdbe.org/6fp1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fp1 RCSB], [http://www.ebi.ac.uk/pdbsum/6fp1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fp1 ProSAT]</span></td></tr> | ||
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<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| - | + | 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. | |
| - | + | 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> | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 6fp1" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6fp1" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Monooxygenase 3D structures|Monooxygenase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Bacillus fluorescens liquefaciens flugge 1886]] | ||
[[Category: Kynurenine 3-monooxygenase]] | [[Category: Kynurenine 3-monooxygenase]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
Revision as of 07:06, 4 March 2020
The crystal structure of P.fluorescens Kynurenine 3-monooxygenase (KMO) in complex with competitive inhibitor No. 1
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