PDBsum entry 2r5c

Transferase

PDB id: 2r5c

Contents

Protein chains

419 a.a. *

Ligands

C6P

Waters ×468

* Residue conservation analysis

PDB id:

2r5c

Name:

Transferase

Title:

Aedes kynurenine aminotransferase in complex with cysteine

Structure:

Kynurenine aminotransferase. Chain: a. Engineered: yes. Other_details: llp at position 255. Kynurenine aminotransferase. Chain: b. Engineered: yes. Other_details: lys at position 255

Source:

Aedes aegypti. Yellow fever mosquito. Organism_taxid: 7159. Strain: liverpool. Gene: kat. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

Resolution:

1.96Å R-factor: 0.222 R-free: 0.267

Authors:

Q.Han,Y.G.Gao,H.Robinson,J.Li

Key ref:

Q.Han et al. (2008). Structural insight into the mechanism of substrate specificity of aedes kynurenine aminotransferase. Biochemistry, 47, 1622-1630. PubMed id: 18186649

Date:

03-Sep-07 Release date: 18-Mar-08

Protein chains

Q17CS8  (Q17CS8_AEDAE) -  Kynurenine aminotransferase from Aedes aegypti

Seq: 477 a.a.

Struc: 419 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: E.C.2.6.1.63 - kynurenine--glyoxylate transaminase.
• Reaction:
  1. L-kynurenine + glyoxylate = kynurenate + glycine + H2O
  2. 3-hydroxy-L-kynurenine + glyoxylate = xanthurenate + glycine + H2O

L-kynurenine + glyoxylate = kynurenate + glycine + H2O (Bound ligand (Het Group name = C6P) matches with 44.00% similarity)

3-hydroxy-L-kynurenine + glyoxylate = xanthurenate + glycine + H2O (Bound ligand (Het Group name = C6P) matches with 42.31% similarity)

• Enzyme class 2: E.C.2.6.1.7 - kynurenine--oxoglutarate transaminase.

Pathway:

• Reaction: L-kynurenine + 2-oxoglutarate = kynurenate + L-glutamate + H2O
• Cofactor: Pyridoxal 5'-phosphate

Pyridoxal 5'-phosphate (Bound ligand (Het Group name = C6P) matches with 65.22% 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

reference

Biochemistry 47:1622-1630 (2008)

PubMed id: 18186649

Structural insight into the mechanism of substrate specificity of aedes kynurenine aminotransferase.

Q.Han, Y.G.Gao, H.Robinson, J.Li.

ABSTRACT

Aedes aegypti kynurenine aminotransferase (AeKAT) is a multifunctional aminotransferase. It catalyzes the transamination of a number of amino acids and uses many biologically relevant alpha-keto acids as amino group acceptors. AeKAT also is a cysteine S-conjugate beta-lyase. The most important function of AeKAT is the biosynthesis of kynurenic acid, a natural antagonist of NMDA and alpha7-nicotinic acetylcholine receptors. Here, we report the crystal structures of AeKAT in complex with its best amino acid substrates, glutamine and cysteine. Glutamine is found in both subunits of the biological dimer, and cysteine is found in one of the two subunits. Both substrates form external aldemines with pyridoxal 5-phosphate in the structures. This is the first instance in which one pyridoxal 5-phosphate enzyme has been crystallized with cysteine or glutamine forming external aldimine complexes, cysteinyl aldimine and glutaminyl aldimine. All the units with substrate are in the closed conformation form, and the unit without substrate is in the open form, which suggests that the binding of substrate induces the conformation change of AeKAT. By comparing the active site residues of the AeKAT-cysteine structure with those of the human KAT I-phenylalanine structure, we determined that Tyr286 in AeKAT is changed to Phe278 in human KAT I, which may explain why AeKAT transaminates hydrophilic amino acids more efficiently than human KAT I does.