3e9k

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{{STRUCTURE_3e9k| PDB=3e9k | SCENE= }}
 
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===Crystal structure of Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex===
 
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{{ABSTRACT_PUBMED_19143568}}
 
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==Disease==
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==Crystal structure of Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex==
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[[http://www.uniprot.org/uniprot/KYNU_HUMAN KYNU_HUMAN]] Note=Xanthurenic aciduria manifesting as massive urinary excretion of large amounts of kynurenine, 3-hydroxykynurenine and xanthurenic acid has been observed in an individual carrying a homozygous missense change in KYNU (PubMed:17334708). The urinary pattern in the patient suggests kynureninase deficiency and a block in the conversion of kynurenine and 3-hydroxykynurenine to anthranilate and 3-hydroxyanthranilate, respectively.[HAMAP-Rule:MF_03017]
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<StructureSection load='3e9k' size='340' side='right'caption='[[3e9k]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3e9k]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E9K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E9K FirstGlance]. <br>
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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]] 1.7&#8491;</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=3XH:3-HYDROXYHIPPURIC+ACID'>3XH</scene>, <scene name='pdbligand=CSX:S-OXY+CYSTEINE'>CSX</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></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=3e9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e9k OCA], [https://pdbe.org/3e9k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e9k RCSB], [https://www.ebi.ac.uk/pdbsum/3e9k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e9k ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/KYNU_HUMAN KYNU_HUMAN] Note=Xanthurenic aciduria manifesting as massive urinary excretion of large amounts of kynurenine, 3-hydroxykynurenine and xanthurenic acid has been observed in an individual carrying a homozygous missense change in KYNU (PubMed:17334708). The urinary pattern in the patient suggests kynureninase deficiency and a block in the conversion of kynurenine and 3-hydroxykynurenine to anthranilate and 3-hydroxyanthranilate, respectively.[HAMAP-Rule:MF_03017]
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== Function ==
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[https://www.uniprot.org/uniprot/KYNU_HUMAN KYNU_HUMAN] Catalyzes the cleavage of L-kynurenine (L-Kyn) and L-3-hydroxykynurenine (L-3OHKyn) into anthranilic acid (AA) and 3-hydroxyanthranilic acid (3-OHAA), respectively. Has a preference for the L-3-hydroxy form. Also has cysteine-conjugate-beta-lyase activity.[HAMAP-Rule:MF_03017]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e9/3e9k_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3e9k ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Homo sapiens kynureninase is a pyridoxal-5'-phosphate dependent enzyme that catalyzes the hydrolytic cleavage of 3-hydroxykynurenine to yield 3-hydroxyanthranilate and L-alanine as part of the tryptophan catabolic pathway leading to the de novo biosynthesis of NAD(+). This pathway results in quinolinate, an excitotoxin that is an NMDA receptor agonist. High levels of quinolinate have been correlated with the etiology of neurodegenerative disorders such as AIDS-related dementia and Alzheimer's disease. We have synthesized a novel kynureninase inhibitor, 3-hydroxyhippurate, cocrystallized it with human kynureninase, and solved the atomic structure. On the basis of an analysis of the complex, we designed a series of His-102, Ser-332, and Asn-333 mutants. The H102W/N333T and H102W/S332G/N333T mutants showed complete reversal of substrate specificity between 3-hydroxykynurenine and L-kynurenine, thus defining the primary residues contributing to substrate specificity in kynureninases.
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==Function==
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Crystal structure of the Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex: insights into the molecular basis of kynureninase substrate specificity.,Lima S, Kumar S, Gawandi V, Momany C, Phillips RS J Med Chem. 2009 Jan 22;52(2):389-96. PMID:19143568<ref>PMID:19143568</ref>
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[[http://www.uniprot.org/uniprot/KYNU_HUMAN KYNU_HUMAN]] Catalyzes the cleavage of L-kynurenine (L-Kyn) and L-3-hydroxykynurenine (L-3OHKyn) into anthranilic acid (AA) and 3-hydroxyanthranilic acid (3-OHAA), respectively. Has a preference for the L-3-hydroxy form. Also has cysteine-conjugate-beta-lyase activity.[HAMAP-Rule:MF_03017]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3e9k]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E9K OCA].
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</div>
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<div class="pdbe-citations 3e9k" style="background-color:#fffaf0;"></div>
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==Reference==
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== References ==
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<ref group="xtra">PMID:019143568</ref><references group="xtra"/><references/>
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Kynureninase]]
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[[Category: Large Structures]]
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[[Category: Gawandi, V.]]
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[[Category: Gawandi V]]
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[[Category: Kumar, S.]]
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[[Category: Kumar S]]
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[[Category: Lima, S.]]
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[[Category: Lima S]]
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[[Category: Momany, C.]]
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[[Category: Momany C]]
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[[Category: Phillips, R S.]]
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[[Category: Phillips RS]]
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[[Category: 3-hydroxy hippurate]]
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[[Category: 3-hydroxyhippuric acid]]
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[[Category: Hydrolase]]
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[[Category: Inhibitor complex]]
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[[Category: Kynureninase]]
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[[Category: Kynurenine hydrolase]]
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[[Category: Kynurenine-l-hydrolase]]
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[[Category: Plp]]
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[[Category: Pyridine nucleotide biosynthesis]]
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[[Category: Pyridoxal phosphate]]
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[[Category: Pyridoxal-5'-phosphate]]
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Current revision

Crystal structure of Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex

PDB ID 3e9k

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