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3e9k

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Revision as of 21:53, 2 December 2018

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

Structural highlights

3e9k is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Related:	2hzp, 1qz9
Gene:	KYNU (HUMAN)
Activity:	Kynureninase, with EC number 3.7.1.3
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[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

[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

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Lima S, Kumar S, Gawandi V, Momany C, Phillips RS. Crystal structure of the Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex: insights into the molecular basis of kynureninase substrate specificity. J Med Chem. 2009 Jan 22;52(2):389-96. PMID:19143568 doi:10.1021/jm8010806

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3e9k"

@@ Line 1: / Line 1: @@
 ==Crystal structure of Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex==
 <StructureSection load='3e9k' size='340' side='right' caption='[[3e9k]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
@@ Line 8: / Line 9: @@
 <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 HUMAN])</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://pdbe.org/3e9k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3e9k RCSB], [http://www.ebi.ac.uk/pdbsum/3e9k PDBsum]</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://pdbe.org/3e9k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3e9k RCSB], [http://www.ebi.ac.uk/pdbsum/3e9k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3e9k ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 18: / Line 19: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e9/3e9k_consurf.spt"</scriptWhenChecked>
+    <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>

3e9k

From Proteopedia

Revision as of 21:53, 2 December 2018

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

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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