5x6r
From Proteopedia
(Difference between revisions)
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<StructureSection load='5x6r' size='340' side='right' caption='[[5x6r]], [[Resolution|resolution]] 1.91Å' scene=''> | <StructureSection load='5x6r' size='340' side='right' caption='[[5x6r]], [[Resolution|resolution]] 1.91Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5x6r]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X6R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5X6R FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5x6r]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X6R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5X6R 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='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> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5x68|5x68]], [[5x6p|5x6p]], [[5x6q|5x6q]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5x68|5x68]], [[5x6p|5x6p]], [[5x6q|5x6q]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BNA4, YBL098W, YBL0828 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</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=5x6r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x6r OCA], [http://pdbe.org/5x6r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x6r RCSB], [http://www.ebi.ac.uk/pdbsum/5x6r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x6r 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=5x6r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x6r OCA], [http://pdbe.org/5x6r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x6r RCSB], [http://www.ebi.ac.uk/pdbsum/5x6r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x6r ProSAT]</span></td></tr> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/KMO_YEAST KMO_YEAST]] Catalyzes the hydroxylation of L-kynurenine (L-Kyn) to form 3-hydroxy-L-kynurenine (L-3OHKyn). Required for synthesis of quinolinic acid.<ref>PMID:12062417</ref> <ref>PMID:15806102</ref> | [[http://www.uniprot.org/uniprot/KMO_YEAST KMO_YEAST]] Catalyzes the hydroxylation of L-kynurenine (L-Kyn) to form 3-hydroxy-L-kynurenine (L-3OHKyn). Required for synthesis of quinolinic acid.<ref>PMID:12062417</ref> <ref>PMID:15806102</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:29429898</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5x6r" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Baker's yeast]] | ||
[[Category: Kynurenine 3-monooxygenase]] | [[Category: Kynurenine 3-monooxygenase]] | ||
[[Category: Hwang, K Y]] | [[Category: Hwang, K Y]] | ||
Revision as of 07:12, 28 February 2018
Crystal structure of Saccharomyces cerevisiae KMO in complex with Ro 61-8048
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