3DC1

Crystal structure of kynurenine aminotransferase II complex with alpha-ketoglutarate


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.217 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II

Han, Q.Cai, T.Tagle, D.A.Robinson, H.Li, J.

(2008) Biosci Rep 28: 205-215

  • DOI: https://doi.org/10.1042/BSR20080085
  • Primary Citation of Related Structures:  
    3DC1

  • PubMed Abstract: 

    KAT (kynurenine aminotransferase) II is a primary enzyme in the brain for catalysing the transamination of kynurenine to KYNA (kynurenic acid). KYNA is the only known endogenous antagonist of the N-methyl-D-aspartate receptor. The enzyme also catalyses the transamination of aminoadipate to alpha-oxoadipate; therefore it was initially named AADAT (aminoadipate aminotransferase). As an endotoxin, aminoadipate influences various elements of glutamatergic neurotransmission and kills primary astrocytes in the brain. A number of studies dealing with the biochemical and functional characteristics of this enzyme exist in the literature, but a systematic assessment of KAT II addressing its substrate profile and kinetic properties has not been performed. The present study examines the biochemical and structural characterization of a human KAT II/AADAT. Substrate screening of human KAT II revealed that the enzyme has a very broad substrate specificity, is capable of catalysing the transamination of 16 out of 24 tested amino acids and could utilize all 16 tested alpha-oxo acids as amino-group acceptors. Kinetic analysis of human KAT II demonstrated its catalytic efficiency for individual amino-group donors and acceptors, providing information as to its preferred substrate affinity. Structural analysis of the human KAT II complex with alpha-oxoglutaric acid revealed a conformational change of an N-terminal fraction, residues 15-33, that is able to adapt to different substrate sizes, which provides a structural basis for its broad substrate specificity.


  • Organizational Affiliation

    Department of Biochemistry, Virginia Tech, Blacksburg, VA 24061, U.S.A. qianhan@vt.edu


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Kynurenine/alpha-aminoadipate aminotransferase mitochondrial
A, B, C, D
425Homo sapiensMutation(s): 0 
Gene Names: AADATKAT2
EC: 2.6.1.7 (PDB Primary Data), 2.6.1.39 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for Q8N5Z0 (Homo sapiens)
Explore Q8N5Z0 
Go to UniProtKB:  Q8N5Z0
PHAROS:  Q8N5Z0
GTEx:  ENSG00000109576 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8N5Z0
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.217 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 60.93α = 89.97
b = 72.09β = 100.65
c = 109.079γ = 93.88
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data collection
HKL-2000data reduction
HKL-2000data scaling
PHASESphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-07-29
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.2: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 1.3: 2023-11-15
    Changes: Data collection