PDBsum entry 3e9k

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protein ligands links
Hydrolase PDB id
Protein chain
446 a.a. *
Waters ×632
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of homo sapiens kynureninase-3-hydroxyhipp inhibitor complex
Structure: Kynureninase. Chain: a. Synonym: l-kynurenine hydrolase. Engineered: yes
Source: Homo sapiens. Organism_taxid: 9606. Gene: kynu. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.70Å     R-factor:   0.155     R-free:   0.191
Authors: S.Lima,S.Kumar,V.Gawandi,C.Momany,R.S.Phillips
Key ref: S.Lima et al. (2009). Crystal structure of the Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex: insights into the molecular basis of kynureninase substrate specificity. J Med Chem, 52, 389-396. PubMed id: 19143568 DOI: 10.1021/jm8010806
22-Aug-08     Release date:   09-Dec-08    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q16719  (KYNU_HUMAN) -  Kynureninase
465 a.a.
446 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Kynureninase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Tryptophan Catabolism
      Reaction: L-kynurenine + H2O = anthranilate + L-alanine
+ H(2)O
= anthranilate
+ L-alanine
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Bound ligand (Het Group name = PLP) matches with 93.75% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   3 terms 
  Biological process     metabolic process   14 terms 
  Biochemical function     catalytic activity     5 terms  


DOI no: 10.1021/jm8010806 J Med Chem 52:389-396 (2009)
PubMed id: 19143568  
Crystal structure of the Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex: insights into the molecular basis of kynureninase substrate specificity.
S.Lima, S.Kumar, V.Gawandi, C.Momany, R.S.Phillips.
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.

Literature references that cite this PDB file's key reference

  PubMed id Reference
23237916 L.Vécsei, L.Szalárdy, F.Fülöp, and J.Toldi (2012).
Kynurenines in the CNS: recent advances and new questions.
  Nat Rev Drug Discov, 12, 64-82.  
19394403 R.Schwarcz, P.Guidetti, K.V.Sathyasaikumar, and P.J.Muchowski (2010).
Of mice, rats and men: Revisiting the quinolinic acid hypothesis of Huntington's disease.
  Prog Neurobiol, 90, 230-245.  
20304989 U.Keller, M.Lang, I.Crnovcic, F.Pfennig, and F.Schauwecker (2010).
The actinomycin biosynthetic gene cluster of Streptomyces chrysomallus: a genetic hall of mirrors for synthesis of a molecule with mirror symmetry.
  J Bacteriol, 192, 2583-2595.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.