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| | ==Crystal structure of Pseudomonas fluorescens KMO in complex with Ro 61-8048== | | ==Crystal structure of Pseudomonas fluorescens KMO in complex with Ro 61-8048== |
| - | <StructureSection load='5x6q' size='340' side='right' caption='[[5x6q]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='5x6q' size='340' side='right'caption='[[5x6q]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5x6q]] is a 1 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=5X6Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5X6Q FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5x6q]] is a 1 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=5X6Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5X6Q FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7ZR:3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzenesulfonamide'>7ZR</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.897Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5x68|5x68]], [[5x6p|5x6p]], [[5x6r|5x6r]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7ZR:3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzenesulfonamide'>7ZR</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5x6q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x6q OCA], [https://pdbe.org/5x6q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5x6q RCSB], [https://www.ebi.ac.uk/pdbsum/5x6q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5x6q ProSAT]</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=5x6q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x6q OCA], [http://pdbe.org/5x6q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x6q RCSB], [http://www.ebi.ac.uk/pdbsum/5x6q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x6q ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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. | + | [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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5x6q" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5x6q" 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: Large Structures]] |
| - | [[Category: Kynurenine 3-monooxygenase]] | + | [[Category: Pseudomonas fluorescens]] |
| - | [[Category: Hwang, K Y]] | + | [[Category: Hwang KY]] |
| - | [[Category: Kim, H T]] | + | [[Category: Kim HT]] |
| - | [[Category: Monoxygenase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
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.
Publication Abstract from PubMed
Kynurenine 3-monooxygenase (KMO) inhibitors have been developed for the treatment of neurodegenerative disorders. The mechanisms of flavin reduction and hydrogen peroxide production by KMO inhibitors are unknown. Herein, we report the structure of human KMO and crystal structures of Saccharomyces cerevisiae (sc) and Pseudomonas fluorescens (pf) KMO with Ro 61-8048. Proton transfer in the hydrogen bond network triggers flavin reduction in p-hydroxybenzoate hydroxylase, but the mechanism triggering flavin reduction in KMO is different. Conformational changes via pi-pi interactions between the loop above the flavin and substrate or non-substrate effectors lead to disorder of the C-terminal alpha helix in scKMO and shifts of domain III in pfKMO, stimulating flavin reduction. Interestingly, Ro 61-8048 has two different binding modes. It acts as a competitive inhibitor in scKMO and as a non-substrate effector in pfKMO. These findings provide understanding of the catalytic cycle of KMO and insight for structure-based drug design of KMO inhibitors.
Structural Basis for Inhibitor-Induced Hydrogen Peroxide Production by Kynurenine 3-Monooxygenase.,Kim HT, Na BK, Chung J, Kim S, Kwon SK, Cha H, Son J, Cho JM, Hwang KY Cell Chem Biol. 2018 Feb 1. pii: S2451-9456(18)30030-8. doi:, 10.1016/j.chembiol.2018.01.008. PMID:29429898[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kim HT, Na BK, Chung J, Kim S, Kwon SK, Cha H, Son J, Cho JM, Hwang KY. Structural Basis for Inhibitor-Induced Hydrogen Peroxide Production by Kynurenine 3-Monooxygenase. Cell Chem Biol. 2018 Feb 1. pii: S2451-9456(18)30030-8. doi:, 10.1016/j.chembiol.2018.01.008. PMID:29429898 doi:http://dx.doi.org/10.1016/j.chembiol.2018.01.008
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