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BioAssay: AID 349604

Inhibition of human recombinant KAT1 expressed in Sf9 cells

Human kynurenine aminotransferase I (hKAT I) catalyzes the formation of kynurenic acid, a neuroactive compound. Here, we report three high-resolution crystal structures (1.50-1.55 A) of hKAT I that are in complex with glycerol and each of two inhibitors of hKAT I: indole-3-acetic acid (IAC) and Tris. Because Tris is able to occupy the substrate binding position, we speculate that this may be the more ..
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 Tested Compounds
 Tested Compounds
All(6)
 
 
Active(4)
 
 
Unspecified(2)
 
 
 Tested Substances
 Tested Substances
All(6)
 
 
Active(4)
 
 
Unspecified(2)
 
 
AID: 349604
Data Source: ChEMBL (497633)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-26
Modify Date: 2014-05-16

Data Table ( Complete ):           Active    All
Target
Sequence: RecName: Full=Kynurenine--oxoglutarate transaminase 1; AltName: Full=Cysteine-S-conjugate beta-lyase; AltName: Full=Glutamine transaminase K; Short=GTK; AltName: Full=Glutamine--phenylpyruvate transaminase; AltName: Full=Kynurenine aminotransferase I; Short=KATI; AltName: Full=Kynurenine--oxoglutarate transaminase I
Description ..   
Protein Family: AAT_like
Comment ..   

Gene:CCBL1     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 4
Description:
Title: Structural insight into the inhibition of human kynurenine aminotransferase I/glutamine transaminase K.

Abstract: Human kynurenine aminotransferase I (hKAT I) catalyzes the formation of kynurenic acid, a neuroactive compound. Here, we report three high-resolution crystal structures (1.50-1.55 A) of hKAT I that are in complex with glycerol and each of two inhibitors of hKAT I: indole-3-acetic acid (IAC) and Tris. Because Tris is able to occupy the substrate binding position, we speculate that this may be the basis for hKAT I inhibition. Furthermore, the hKAT/IAC complex structure reveals that the binding moieties of the inhibitor are its indole ring and a carboxyl group. Six chemicals with both binding moieties were tested for their ability to inhibit hKAT I activity; 3-indolepropionic acid and DL-indole-3-lactic acid demonstrated the highest level of inhibition, and as they cannot be considered as substrates of the enzyme, these two inhibitors are promising candidates for future study. Perhaps even more significantly, we report the discovery of two different ligands located simultaneously in the hKAT I active center for the first time.
(PMID: 19338303)
Categorized Comment
Assay Type: Binding

Assay Data Source: Scientific Literature

Assay Test Type: In vitro

BAO: Assay Format: cell-based format

Assay Cell Type: Sf9

Target Type: Target is a single protein chain

Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
2Activity activity commentActivity activity commentString
3Activity standard flagActivity standard flagInteger
4Activity qualifierActivity qualifierString
5Activity published valueActivity published valueFloat
6Activity standard valueActivity standard valueFloat
7Activity data validityActivity data validityString
8Activity binding domainsActivity binding domainsString
9IC50 activity commentIC50 activity commentString
10IC50 standard flagIC50 standard flagInteger
11IC50 qualifierIC50 qualifierString
12IC50 published valueIC50 published valueFloatmM
13IC50 standard valueIC50 standard valueFloatnM
14IC50 data validityIC50 data validityString
15IC50 binding domainsIC50 binding domainsString

* Activity Concentration.

Data Table (Concise)
Classification
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