PDBsum entry 2r2n

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protein ligands Protein-protein interface(s) links
Transferase PDB id
Protein chains
425 a.a. *
PMP ×4
KYN ×4
GOL ×6
Waters ×1341
* Residue conservation analysis
PDB id:
Name: Transferase
Title: The crystal structure of human kynurenine aminotransferase i complex with kynurenine
Structure: Kynurenine/alpha-aminoadipate aminotransferase mitochondrial. Chain: a, b, c, d. Synonym: kat/aadat, kynurenine--oxoglutarate transaminase i kynurenine aminotransferase ii, kynurenine--oxoglutarate aminotransferase ii, 2-aminoadipate transaminase, 2- aminoa aminotransferase, alpha-aminoadipate aminotransferase, aada engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: aadat, kat2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
1.95Å     R-factor:   0.196     R-free:   0.223
Authors: Q.Han,H.Robinson,J.Li
Key ref:
Q.Han et al. (2008). Crystal Structure of Human Kynurenine Aminotransferase II. J Biol Chem, 283, 3567-3573. PubMed id: 18056995 DOI: 10.1074/jbc.M708358200
27-Aug-07     Release date:   04-Dec-07    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q8N5Z0  (AADAT_HUMAN) -  Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial
425 a.a.
425 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: E.C.  - 2-aminoadipate transaminase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Lysine catabolism
      Reaction: L-2-aminoadipate + 2-oxoglutarate = 2-oxoadipate + L-glutamate
Bound ligand (Het Group name = KYN)
matches with 52.94% similarity
+ 2-oxoglutarate
= 2-oxoadipate
+ L-glutamate
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Bound ligand (Het Group name = PMP) matches with 88.24% similarity
   Enzyme class 2: E.C.  - Kynurenine--oxoglutarate transaminase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Reaction: L-kynurenine + 2-oxoglutarate = 4-(2-aminophenyl)-2,4-dioxobutanoate + L-glutamate
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
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   2 terms 
  Biological process     small molecule metabolic process   11 terms 
  Biochemical function     catalytic activity     7 terms  


DOI no: 10.1074/jbc.M708358200 J Biol Chem 283:3567-3573 (2008)
PubMed id: 18056995  
Crystal Structure of Human Kynurenine Aminotransferase II.
Q.Han, H.Robinson, J.Li.
Human kynurenine aminotransferase II (hKAT-II) efficiently catalyzes the transamination of knunrenine to kynurenic acid (KYNA). KYNA is the only known endogenous antagonist of N-methyl-d-aspartate (NMDA) receptors and is also an antagonist of 7-nicotinic acetylcholine receptors. Abnormal concentrations of brain KYNA have been implicated in the pathogenesis and development of several neurological and psychiatric diseases in humans. Consequently, enzymes involved in the production of brain KYNA have been considered potential regulatory targets. In this article, we report a 2.16A crystal structure of hKAT-II and a 1.95A structure of its complex with kynurenine. The protein architecture of hKAT-II reveals that it belongs to the fold-type I pyridoxal 5-phosphate (PLP)-dependent enzymes. In comparison with all subclasses of fold-type I-PLP-dependent enzymes, we propose that hKAT-II represents a novel subclass in the fold-type I enzymes because of the unique folding of its first 65 N-terminal residues. This study provides a molecular basis for future effort in maintaining physiological concentrations of KYNA through molecular and biochemical regulation of hKAT-II.
  Selected figure(s)  
Figure 4.
FIGURE 4. The hKAT-II active site. A stereo view of the active site in the hKAT-II structure. The protein portions building up the active site and contributed to by the two subunits of the functional homodimer are shown in a schematic representation and are colored in deep teal (subunit A) and violet (subunit B). The PLP cofactor and the protein residues within a 5-Å distance of PLP are shown. Only the 2F[o]-F[c] electron density map covering the LLP 263 is shown contoured at the 1 sigma.
Figure 6.
FIGURE 6. Conformational changes. Superposition of a subunit of hKAT-II structure (blue) onto a subunit of KAT-II: kynurenine complex structure (green). The protein residues within 4 Å of kynurenine are depicted as sticks, and protein residues 16-31 are shown in a schematic representation. The residues and ligand from hKAT-II native structure are shown in green, and those from the complex structure are in blue.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2008, 283, 3567-3573) copyright 2008.  
  Figures were selected by an automated process.  

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
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.  
19941066 T.Ogaya, Z.Song, K.Ishii, and T.Fukushima (2010).
Changes in extracellular kynurenic acid concentrations in rat prefrontal cortex after D-kynurenine infusion: an in vivo microdialysis study.
  Neurochem Res, 35, 559-563.  
19381689 B.Battsetseg, D.Boldbaatar, B.Battur, X.Xuan, and K.Fujisaki (2009).
Cloning and molecular characterization of tick kynurenine aminotransferase (HlKAT) from Haemaphysalis longicornis (Acari: Ixodidae).
  Parasitol Res, 105, 669-679.  
19029248 Q.Han, H.Robinson, T.Cai, D.A.Tagle, and J.Li (2009).
Biochemical and structural properties of mouse kynurenine aminotransferase III.
  Mol Cell Biol, 29, 784-793.
PDB codes: 3e2f 3e2y 3e2z
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
18831049 T.Tomita, T.Miyagawa, T.Miyazaki, S.Fushinobu, T.Kuzuyama, and M.Nishiyama (2009).
Mechanism for multiple-substrates recognition of alpha-aminoadipate aminotransferase from Thermus thermophilus.
  Proteins, 75, 348-359.
PDB codes: 2zp7 3cbf
18950711 F.Rossi, R.Schwarcz, and M.Rizzi (2008).
Curiosity to kill the KAT (kynurenine aminotransferase): structural insights into brain kynurenic acid synthesis.
  Curr Opin Struct Biol, 18, 748-755.  
18620547 Q.Han, T.Cai, D.A.Tagle, H.Robinson, and J.Li (2008).
Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II.
  Biosci Rep, 28, 205-215.
PDB code: 3dc1
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.