5y77: Difference between revisions
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==Crystal structure of Pseudomonas fluorescens Kynurenine 3-monooxygenase in complex with L-KYN (seMet derivative)== | ==Crystal structure of Pseudomonas fluorescens Kynurenine 3-monooxygenase in complex with L-KYN (seMet derivative)== | ||
<StructureSection load='5y77' size='340' side='right' caption='[[5y77]], [[Resolution|resolution]] 1.60Å' scene=''> | <StructureSection load='5y77' size='340' side='right'caption='[[5y77]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5y77]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5y77]] 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=5Y77 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5Y77 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=KYN:(2S)-2-AMINO-4-(2-AMINOPHENYL)-4-OXOBUTANOIC+ACID'>KYN</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=5y77 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y77 OCA], [https://pdbe.org/5y77 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5y77 RCSB], [https://www.ebi.ac.uk/pdbsum/5y77 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5y77 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [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 5y77" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5y77" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Monooxygenase 3D structures|Monooxygenase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Pseudomonas fluorescens]] | ||
[[Category: Gao | [[Category: Gao JJ]] | ||
[[Category: Xiang | [[Category: Xiang Y]] | ||
[[Category: Zhu | [[Category: Zhu DY]] | ||
Latest revision as of 15:21, 6 November 2024
Crystal structure of Pseudomonas fluorescens Kynurenine 3-monooxygenase in complex with L-KYN (seMet derivative)Crystal structure of Pseudomonas fluorescens Kynurenine 3-monooxygenase in complex with L-KYN (seMet derivative)
Structural highlights
FunctionKMO_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 PubMedThe human kynurenine 3-monooxygenase (hKMO) is a potential therapeutic target for neurodegenerative and neurologic disorders. Inhibition of KMO by Ro 61-8048, a potent, selective, and the most widely used inhibitor of KMO, was shown effective in various models of neurodegenerative or neurologic disorders. However, the molecular basis of hKMO inhibition by Ro 61-8048 is not clearly understood. Here, we report biochemistry studies on hKMO and crystal structures of an hKMO homolog, pfKMO from Pseudomonas fluorescens, in complex with the substrate l-kynurenine and Ro 61-8048. We found that the C-terminal approximately 110 aa are essential for the enzymatic activity of hKMO and the homologous C-terminal region of pfKMO folds into a distinct, all-alpha-helical domain, which associates with the N-terminal catalytic domain to form a unique tunnel in proximity to the substrate-binding pocket. The tunnel binds the Ro 61-8048 molecule, which fills most of the tunnel, and Ro 61-8048 is hydrogen bonded with several completely conserved residues, including an essential catalytic residue. Modification of Ro 61-8048 and biochemical studies of the modified Ro 61-8048 derivatives suggested that Ro 61-8048 inhibits the enzyme in an allosteric manner by affecting the conformation of the essential catalytic residue and by blocking entry of the substrate or product release. The unique binding sites distinguish Ro 61-8048 as a noncompetitive and highly selective inhibitor from other competitive inhibitors, which should facilitate further optimization of Ro 61-8048 and the development of new inhibitory drugs to hKMO.-Gao, J., Yao, L., Xia, T., Liao, X., Zhu, D., Xiang, Y. Biochemistry and structural studies of kynurenine 3-monooxygenase reveal allosteric inhibition by Ro 61-8048. Biochemistry and structural studies of kynurenine 3-monooxygenase reveal allosteric inhibition by Ro 61-8048.,Gao J, Yao L, Xia T, Liao X, Zhu D, Xiang Y FASEB J. 2017 Dec 5. pii: fj.201700397RR. doi: 10.1096/fj.201700397RR. PMID:29208702[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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