3e9k: Difference between revisions
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==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 [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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3E9K FirstGlance]. <br> | |||
==Disease== | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3XH:3-HYDROXYHIPPURIC+ACID'>3XH</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr> | ||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSX:S-OXY+CYSTEINE'>CSX</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2hzp|2hzp]], [[1qz9|1qz9]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KYNU ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Kynureninase Kynureninase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.7.1.3 3.7.1.3] </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=3e9k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e9k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3e9k RCSB], [http://www.ebi.ac.uk/pdbsum/3e9k PDBsum]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[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] | [[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] | ||
== Function == | |||
==Function== | |||
[[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] | [[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] | ||
== 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/chain_selection.php?pdb_ID=2ata 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> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Kynureninase]] | [[Category: Kynureninase]] | ||
[[Category: Gawandi, V | [[Category: Gawandi, V]] | ||
[[Category: Kumar, S | [[Category: Kumar, S]] | ||
[[Category: Lima, S | [[Category: Lima, S]] | ||
[[Category: Momany, C | [[Category: Momany, C]] | ||
[[Category: Phillips, R S | [[Category: Phillips, R S]] | ||
[[Category: 3-hydroxy hippurate]] | [[Category: 3-hydroxy hippurate]] | ||
[[Category: 3-hydroxyhippuric acid]] | [[Category: 3-hydroxyhippuric acid]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Inhibitor complex]] | [[Category: Inhibitor complex]] | ||
[[Category: Kynurenine hydrolase]] | [[Category: Kynurenine hydrolase]] | ||
[[Category: Kynurenine-l-hydrolase]] | [[Category: Kynurenine-l-hydrolase]] | ||
