PDBsum entry 1w7m

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protein ligands links
Transferase PDB id
Protein chain
415 a.a. *
Waters ×202
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of human kynurenine aminotransferase i in complex with l-phe
Structure: Kynurenine--oxoglutarate transaminase i. Chain: a. Synonym: kynurenine aminotransferase i, kati, glutamine-phenylpyruvate transaminase, glutamine transaminase k, gtk, cysteine-s-conjugate beta-lyase. Engineered: yes
Source: Homo sapiens. Human. Organ: liver. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Biol. unit: Dimer (from PDB file)
2.70Å     R-factor:   0.178     R-free:   0.232
Authors: F.Rossi,Q.Han,J.Li,J.Li,M.Rizzi
Key ref:
F.Rossi et al. (2004). Crystal structure of human kynurenine aminotransferase I. J Biol Chem, 279, 50214-50220. PubMed id: 15364907 DOI: 10.1074/jbc.M409291200
06-Sep-04     Release date:   08-Sep-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q16773  (KAT1_HUMAN) -  Kynurenine--oxoglutarate transaminase 1
422 a.a.
415 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class 1: E.C.  - Glutamine--phenylpyruvate transaminase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: L-glutamine + phenylpyruvate = 2-oxoglutaramate + L-phenylalanine
+ phenylpyruvate
= 2-oxoglutaramate
Bound ligand (Het Group name = DPN)
corresponds exactly
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
   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 = DPN)
matches with 80.00% similarity
+ 2-oxoglutarate
= 4-(2-aminophenyl)-2,4-dioxobutanoate
+ L-glutamate
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
   Enzyme class 3: E.C.  - Cysteine-S-conjugate beta-lyase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: RS-CH2-CH(NH3(+))COO- + H2O = RSH + NH(3) + pyruvate
Bound ligand (Het Group name = DPN)
matches with 42.00% similarity
+ H(2)O
+ NH(3)
+ pyruvate
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
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     cytoplasm   4 terms 
  Biological process     small molecule metabolic process   9 terms 
  Biochemical function     catalytic activity     12 terms  


DOI no: 10.1074/jbc.M409291200 J Biol Chem 279:50214-50220 (2004)
PubMed id: 15364907  
Crystal structure of human kynurenine aminotransferase I.
F.Rossi, Q.Han, J.Li, J.Li, M.Rizzi.
The kynurenine pathway has long been regarded as a valuable target for the treatment of several neurological disorders accompanied by unbalanced levels of metabolites along the catabolic cascade, kynurenic acid among them. The irreversible transamination of kynurenine is the sole source of kynurenic acid, and it is catalyzed by different isoforms of the 5'-pyridoxal phosphate-dependent kynurenine aminotransferase (KAT). The KAT-I isozyme has also been reported to possess beta-lyase activity toward several sulfur- and selenium-conjugated molecules, leading to the proposal of a role of the enzyme in carcinogenesis associated with environmental pollutants. We solved the structure of human KAT-I in its 5'-pyridoxal phosphate and pyridoxamine phosphate forms and in complex with the competing substrate l-Phe. The enzyme active site revealed a striking crown of aromatic residues decorating the ligand binding pocket, which we propose as a major molecular determinant for substrate recognition. Ligand-induced conformational changes affecting Tyr(101) and the Trp(18)-bearing alpha-helix H1 appear to play a central role in catalysis. Our data reveal a key structural role of Glu(27), providing a molecular basis for the reported loss of enzymatic activity displayed by the equivalent Glu --> Gly mutation in KAT-I of spontaneously hypertensive rats.
  Selected figure(s)  
Figure 1.
FIG. 1. Scheme of the two-step reaction catalyzed by kynurenine aminotransferases. The first half of the reaction is fully irreversible.
Figure 6.
FIG. 6. Ribbon representation of the hKAT-I subunit underlining the proposed structural role of Glu27 located at the C terminus of helix H1. In rat kynurenine aminotransferase, the indicated mutation (Glu Gly) results in an hypertensive phenotype. PLP molecule and amino acid residues are drawn as a ball-and-stick representation. The N-terminal arm and the helix H1 are colored in green.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 50214-50220) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20306345 A.J.Cooper, B.F.Krasnikov, Z.V.Niatsetskaya, J.T.Pinto, P.S.Callery, M.T.Villar, A.Artigues, and S.A.Bruschi (2011).
Cysteine S-conjugate β-lyases: important roles in the metabolism of naturally occurring sulfur and selenium-containing compounds, xenobiotics and anticancer agents.
  Amino Acids, 41, 7.  
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
20872665 K.Ishii, T.Ogaya, Z.Song, H.Iizuka, and T.Fukushima (2010).
Changes in the plasma concentrations of D-kynurenine and kynurenic acid in rats after intraperitoneal administration of tryptophan enantiomers.
  Chirality, 22, 901-906.  
  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.  
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.  
19584079 J.I.Lee, H.Nian, A.J.Cooper, R.Sinha, J.Dai, W.H.Bisson, R.H.Dashwood, and J.T.Pinto (2009).
Alpha-keto acid metabolites of naturally occurring organoselenium compounds as inhibitors of histone deacetylase in human prostate cancer cells.
  Cancer Prev Res (Phila), 2, 683-693.  
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
18655158 T.Fukushima, Y.Sone, S.Mitsuhashi, M.Tomiya, and T.Toyo'oka (2009).
Alteration of kynurenic acid concentration in rat plasma following optically pure kynurenine administration: a comparative study between enantiomers.
  Chirality, 21, 468-472.  
18342615 A.J.Cooper, J.T.Pinto, B.F.Krasnikov, Z.V.Niatsetskaya, Q.Han, J.Li, D.Vauzour, and J.P.Spencer (2008).
Substrate specificity of human glutamine transaminase K as an aminotransferase and as a cysteine S-conjugate beta-lyase.
  Arch Biochem Biophys, 474, 72-81.  
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
18186649 Q.Han, Y.G.Gao, H.Robinson, and J.Li (2008).
Structural insight into the mechanism of substrate specificity of aedes kynurenine aminotransferase.
  Biochemistry, 47, 1622-1630.
PDB codes: 2r5c 2r5e
17683331 I.Matsui, and K.Harata (2007).
Implication for buried polar contacts and ion pairs in hyperthermostable enzymes.
  FEBS J, 274, 4012-4022.  
16585514 F.Rossi, S.Garavaglia, G.B.Giovenzana, B.Arcà, J.Li, and M.Rizzi (2006).
Crystal structure of the Anopheles gambiae 3-hydroxykynurenine transaminase.
  Proc Natl Acad Sci U S A, 103, 5711-5716.
PDB codes: 2ch1 2ch2
16795038 N.E.Ward, N.R.Pellis, S.A.Risin, and D.Risin (2006).
Gene expression alterations in activated human T-cells induced by modeled microgravity.
  J Cell Biochem, 99, 1187-1202.  
16262702 F.Rossi, F.Lombardo, A.Paglino, C.Cassani, G.Miglio, B.Arcà, and M.Rizzi (2005).
Identification and biochemical characterization of the Anopheles gambiae 3-hydroxykynurenine transaminase.
  FEBS J, 272, 5653-5662.  
  16511030 H.Chon, H.Matsumura, S.Shimizu, N.Maeda, Y.Koga, K.Takano, and S.Kanaya (2005).
Overproduction and preliminary crystallographic study of a human kynurenine aminotransferase II homologue from Pyrococcus horikoshii OT3.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 319-322.  
16138312 H.Chon, H.Matsumura, Y.Koga, K.Takano, and S.Kanaya (2005).
Crystal structure of a human kynurenine aminotransferase II homologue from Pyrococcus horikoshii OT3 at 2.20 A resolution.
  Proteins, 61, 685-688.
PDB code: 1x0m
15853804 Q.Han, Y.G.Gao, H.Robinson, H.Ding, S.Wilson, and J.Li (2005).
Crystal structures of Aedes aegypti kynurenine aminotransferase.
  FEBS J, 272, 2198-2206.
PDB codes: 1yiy 1yiz
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.