PDBsum entry 1yiy

Transferase

PDB id: 1yiy

Contents

Protein chains

418 a.a. *

Ligands

PMP ×2

Metals

_BR ×5

Waters ×440

* Residue conservation analysis

PDB id:

1yiy

Name:

Transferase

Title:

Aedes aegypti kynurenine aminotransferase

Structure:

Kynurenine aminotransferase. Glutamine transaminase k. Chain: a, b. Fragment: kynurenine aminotransferase (residues 49-477). Engineered: yes

Source:

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

Biol. unit:

Dimer (from PQS)

Resolution:

1.90Å R-factor: 0.219 R-free: 0.264

Authors:

Q.Han,Y.G.Gao,H.Robinson,H.Ding,S.Wilson,J.Li

Key ref:

Q.Han et al. (2005). Crystal structures of Aedes aegypti kynurenine aminotransferase. FEBS J, 272, 2198-2206. PubMed id: 15853804 DOI: 10.1111/j.1742-4658.2005.04643.x

Date:

13-Jan-05 Release date: 10-May-05

Protein chains

Q17CS8  (Q17CS8_AEDAE) -  Kynurenine aminotransferase from Aedes aegypti

Seq: 477 a.a.

Struc: 418 a.a.*

* 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.
• 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 = PMP) matches with 57.89% similarity)

3-hydroxy-L-kynurenine + glyoxylate = xanthurenate + glycine + H2O (Bound ligand (Het Group name = PMP) matches with 55.00% 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 = 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

reference

DOI no: 10.1111/j.1742-4658.2005.04643.x

FEBS J 272:2198-2206 (2005)

PubMed id: 15853804

Crystal structures of Aedes aegypti kynurenine aminotransferase.

Q.Han, Y.G.Gao, H.Robinson, H.Ding, S.Wilson, J.Li.

ABSTRACT

Aedes aegypti kynurenine aminotransferase (AeKAT) catalyzes the irreversible transamination of kynurenine to kynurenic acid, the natural antagonist of NMDA and 7-nicotinic acetycholine receptors. Here, we report the crystal structure of AeKAT in its PMP and PLP forms at 1.90 and 1.55 A, respectively. The structure was solved by a combination of single-wavelength anomalous dispersion and molecular replacement approaches. The initial search model in the molecular replacement method was built with the result of single-wavelength anomalous dispersion data from the Br-AeKAT crystal in combination with homology modeling. The solved structure shows that the enzyme is a homodimer, and that the two subunits are stabilized by a number of hydrogen bonds, salts bridges, and hydrophobic interactions. Each subunit is divided into an N-terminal arm and small and large domains. Based on its folding, the enzyme belongs to the prototypical fold type, aminotransferase subgroup I. The three-dimensional structure shows a strictly conserved 'PLP-phosphate binding cup' featuring PLP-dependent enzymes. The interaction between Cys284 (A) and Cys284 (B) is unique in AeKAT, which might explain the cysteine effect of AeKAT activity. Further mutation experiments of this residue are needed to eventually understand the mechanism of the enzyme modulation by cysteine.

Selected figure(s)

Figure 3.
Fig. 3. Diagrams of 2F[o] – F[c] electron density maps for the active sites of the PMP and PLP forms. The map contoured at 2.0 sigma is calculated using data between 10.0 and 1.90 Å and 10.0 and 1.55 Å resolution for the PMP and PLP forms of AeKAT, respectively. (A) PLP form; (B) PMP form.

Figure 4.
Fig. 4. Schematic diagram showing active site interactions in AeKAT. Hydrogen bonds are shown by dotted lines. Phe135 and Val223 sandwich the pyridine ring of PLP. (A) PLP form; (B) PMP form.

The above figures are reprinted by permission from the Federation of European Biochemical Societies: FEBS J (2005, 272, 2198-2206) copyright 2005.

Figures were selected by an automated process.