PDBsum entry: 1w7n

Transferase

PDB id: 1w7n

Contents

Protein chain

415 a.a. *

Ligands

PMP

Waters ×197

* Residue conservation analysis

PDB id:

1w7n

Name:

Transferase

Title:

Crystal structure of human kynurenine aminotransferase i in pmp form

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)

Resolution:

2.90Å R-factor: 0.172 R-free: 0.220

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

Date:

06-Sep-04 Release date: 08-Sep-04

Protein chain

Q16773  (KAT1_HUMAN) -  Kynurenine--oxoglutarate transaminase 1

Seq: 422 a.a.

Struc: 415 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 1: E.C.2.6.1.64 - Glutamine--phenylpyruvate transaminase.
• Reaction: L-glutamine + phenylpyruvate = 2-oxoglutaramate + L-phenylalanine
• Cofactor: Pyridoxal 5'-phosphate

Pyridoxal 5'-phosphate (Bound ligand (Het Group name = PMP) matches with 88.00% similarity)

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

Pathway:

• Reaction: L-kynurenine + 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 88.00% similarity)

• Enzyme class 3: E.C.4.4.1.13 - Cysteine-S-conjugate beta-lyase.
• Reaction: RS-CH₂-CH(NH₃(+))COO^- = RSH + NH(3) + pyruvate
• Cofactor: Pyridoxal 5'-phosphate

Pyridoxal 5'-phosphate (Bound ligand (Het Group name = PMP) matches with 88.00% 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 

• Cellular component: cytoplasm (2 terms)
• Biological process: biosynthetic process (3 terms)
• Biochemical function: catalytic activity (11 terms)

reference

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.

ABSTRACT

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.