3e9k: Difference between revisions
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New page: '''Unreleased structure''' The entry 3e9k is ON HOLD Authors: Lima, S., Kumar, S., Gawandi, V., Momany, C., Phillips, R.S. Description: Crystal structure of Homo sapiens kynureninase-3... |
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The | ==Crystal structure of Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex== | ||
<StructureSection load='3e9k' size='340' side='right'caption='[[3e9k]], [[Resolution|resolution]] 1.70Å' scene=''> | |||
== Structural highlights == | |||
<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> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> | |||
<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> | |||
<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> | |||
</table> | |||
== Disease == | |||
[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] | |||
== Function == | |||
[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] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e9/3e9k_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</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]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3e9k" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Gawandi V]] | |||
[[Category: Kumar S]] | |||
[[Category: Lima S]] | |||
[[Category: Momany C]] | |||
[[Category: Phillips RS]] | |||
