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PDBsum entry 3e2z

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protein ligands Protein-protein interface(s) links
Transferase, lyase PDB id
3e2z
Jmol
Contents
Protein chains
410 a.a. *
Ligands
KYN ×2
GOL ×4
PMP
Waters ×83
* Residue conservation analysis
PDB id:
3e2z
Name: Transferase, lyase
Title: Crystal structure of mouse kynurenine aminotransferase iii i with kynurenine
Structure: Kynurenine-oxoglutarate transaminase 3. Chain: a. Synonym: kynurenine-oxoglutarate transaminase iii, kynureni aminotransferase iii, katiii, cysteine-s-conjugate beta-lya engineered: yes. Kynurenine-oxoglutarate transaminase 3. Chain: b. Synonym: kynurenine-oxoglutarate transaminase iii, kynureni aminotransferase iii, katiii, cysteine-s-conjugate beta-lya
Source: Mus musculus. Organism_taxid: 10090. Gene: ccbl2, kat3. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
2.81Å     R-factor:   0.194     R-free:   0.237
Authors: Q.Han,R.Robinson,T.Cai,D.A.Tagle,J.Li
Key ref: Q.Han et al. (2009). Biochemical and structural properties of mouse kynurenine aminotransferase III. Mol Cell Biol, 29, 784-793. PubMed id: 19029248
Date:
06-Aug-08     Release date:   30-Dec-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q71RI9  (KAT3_MOUSE) -  Kynurenine--oxoglutarate transaminase 3
Seq:
Struc:
455 a.a.
410 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class 1: E.C.2.6.1.63  - Kynurenine--glyoxylate transaminase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: L-kynurenine + glyoxylate = 4-(2-aminophenyl)-2,4-dioxobutanoate + glycine
L-kynurenine
Bound ligand (Het Group name = KYN)
corresponds exactly
+
glyoxylate
Bound ligand (Het Group name = GOL)
matches with 57.14% similarity
= 4-(2-aminophenyl)-2,4-dioxobutanoate
+ glycine
   Enzyme class 2: E.C.2.6.1.7  - Kynurenine--oxoglutarate transaminase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
      Reaction: L-kynurenine + 2-oxoglutarate = 4-(2-aminophenyl)-2,4-dioxobutanoate + L-glutamate
L-kynurenine
Bound ligand (Het Group name = KYN)
corresponds exactly
+ 2-oxoglutarate
= 4-(2-aminophenyl)-2,4-dioxobutanoate
+ L-glutamate
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Bound ligand (Het Group name = PMP) matches with 88.24% similarity
   Enzyme class 3: E.C.4.4.1.13  - Cysteine-S-conjugate beta-lyase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: An L-cysteine-S-conjugate + H2O = RSH + NH3 + pyruvate
L-cysteine-S-conjugate
+ H(2)O
= RSH
+ NH(3)
Bound ligand (Het Group name = GOL)
matches with 71.43% similarity
+ pyruvate
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Bound ligand (Het Group name = PMP) matches with 88.24% similarity
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     mitochondrion   1 term 
  Biological process     L-kynurenine metabolic process   5 terms 
  Biochemical function     catalytic activity     10 terms  

 

 
    reference    
 
 
Mol Cell Biol 29:784-793 (2009)
PubMed id: 19029248  
 
 
Biochemical and structural properties of mouse kynurenine aminotransferase III.
Q.Han, H.Robinson, T.Cai, D.A.Tagle, J.Li.
 
  ABSTRACT  
 
Kynurenine aminotransferase III (KAT III) has been considered to be involved in the production of mammalian brain kynurenic acid (KYNA), which plays an important role in protecting neurons from overstimulation by excitatory neurotransmitters. The enzyme was identified based on its high sequence identity with mammalian KAT I, but its activity toward kynurenine and its structural characteristics have not been established. In this study, the biochemical and structural properties of mouse KAT III (mKAT III) were determined. Specifically, mKAT III cDNA was amplified from a mouse brain cDNA library, and its recombinant protein was expressed in an insect cell protein expression system. We established that mKAT III is able to efficiently catalyze the transamination of kynurenine to KYNA and has optimum activity at relatively basic conditions of around pH 9.0 and at relatively high temperatures of 50 to 60 degrees C. In addition, mKAT III is active toward a number of other amino acids. Its activity toward kynurenine is significantly decreased in the presence of methionine, histidine, glutamine, leucine, cysteine, and 3-hydroxykynurenine. Through macromolecular crystallography, we determined the mKAT III crystal structure and its structures in complex with kynurenine and glutamine. Structural analysis revealed the overall architecture of mKAT III and its cofactor binding site and active center residues. This is the first report concerning the biochemical characteristics and crystal structures of KAT III enzymes and provides a basis toward understanding the overall physiological role of mammalian KAT III in vivo and insight into regulating the levels of endogenous KYNA through modulation of the enzyme in the mouse brain.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21439022 E.Passera, B.Campanini, F.Rossi, V.Casazza, M.Rizzi, R.Pellicciari, and A.Mozzarelli (2011).
Human kynurenine aminotransferase II - reactivity with substrates and inhibitors.
  FEBS J, 278, 1882-1900.  
20977429 Q.Han, H.Robinson, T.Cai, D.A.Tagle, and J.Li (2011).
Biochemical and structural characterization of mouse mitochondrial aspartate aminotransferase, a newly identified kynurenine aminotransferase-IV.
  Biosci Rep, 31, 323-332.
PDB codes: 3pd6 3pdb
20147364 I.Wonodi, and R.Schwarcz (2010).
Cortical kynurenine pathway metabolism: a novel target for cognitive enhancement in Schizophrenia.
  Schizophr Bull, 36, 211-218.  
  21153519 P.Mehere, Q.Han, J.A.Lemkul, C.J.Vavricka, H.Robinson, D.R.Bevan, and J.Li (2010).
Tyrosine aminotransferase: biochemical and structural properties and molecular dynamics simulations.
  Protein Cell, 1, 1023-1032.
PDB code: 3pdx
19826765 Q.Han, T.Cai, D.A.Tagle, and J.Li (2010).
Structure, expression, and function of kynurenine aminotransferases in human and rodent brains.
  Cell Mol Life Sci, 67, 353-368.
PDB code: 3hlm
20482848 Q.Han, T.Cai, D.A.Tagle, and J.Li (2010).
Thermal stability, pH dependence and inhibition of four murine kynurenine aminotransferases.
  BMC Biochem, 11, 19.  
19338303 Q.Han, H.Robinson, T.Cai, D.A.Tagle, and J.Li (2009).
Structural insight into the inhibition of human kynurenine aminotransferase I/glutamine transaminase K.
  J Med Chem, 52, 2786-2793.
PDB codes: 3fvs 3fvu 3fvx
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. Where a reference describes a PDB structure, the PDB codes are shown on the right.