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BioAssay: AID 456232

Activity at human recombinant CES1 expressed in baculovirus-infected Spodoptera frugiperda Sf21 cells assessed as substrate hydrolysis by fluorescence assay

Metabolic problems lead to numerous failures during clinical trials, and much effort is now devoted in developing in silico models predicting metabolic stability and metabolites. Such models are well known for cytochromes P450 and some transferases, whereas little has been done to predict the hydrolytic activity of human hydrolases. The present study was undertaken to develop a computational more ..
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 Tested Compounds
 Tested Compounds
All(39)
 
 
Active(14)
 
 
Unspecified(25)
 
 
 Tested Substances
 Tested Substances
All(39)
 
 
Active(14)
 
 
Unspecified(25)
 
 
 Related BioAssays
 Related BioAssays
AID: 456232
Data Source: ChEMBL (607290)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-07-30
Modify Date: 2014-05-26

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: RecName: Full=Liver carboxylesterase 1; AltName: Full=Acyl-coenzyme A:cholesterol acyltransferase; Short=ACAT; AltName: Full=Brain carboxylesterase hBr1; AltName: Full=Carboxylesterase 1; Short=CE-1; Short=hCE-1; AltName: Full=Cocaine carboxylesterase; AltName: Full=Egasyn; AltName: Full=HMSE; AltName: Full=Methylumbelliferyl-acetate deacetylase 1; AltName: Full=Monocyte/macrophage serine esterase; AltName: Full=Retinyl ester hydrolase; Short=REH; AltName: Full=Serine esterase 1; AltName: Full=Triacylglycerol hydrolase; Short=TGH; Flags: Precursor
Description ..   
Protein Family: Esterase_lipase
Comment ..   

Gene:CES1     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 14
Description:
Title: In silico prediction of human carboxylesterase-1 (hCES1) metabolism combining docking analyses and MD simulations.

Abstract: Metabolic problems lead to numerous failures during clinical trials, and much effort is now devoted in developing in silico models predicting metabolic stability and metabolites. Such models are well known for cytochromes P450 and some transferases, whereas little has been done to predict the hydrolytic activity of human hydrolases. The present study was undertaken to develop a computational approach able to predict the hydrolysis of novel esters by human carboxylesterase hCES1. The study involves both docking analyses of known substrates to develop predictive models, and molecular dynamics (MD) simulations to reveal the in situ behavior of substrates and products, with particular attention being paid to the influence of their ionization state. The results emphasize some crucial properties of the hCES1 catalytic cavity, confirming that as a trend with several exceptions, hCES1 prefers substrates with relatively smaller and somewhat polar alkyl/aryl groups and larger hydrophobic acyl moieties. The docking results underline the usefulness of the hydrophobic interaction score proposed here, which allows a robust prediction of hCES1 catalysis, while the MD simulations show the different behavior of substrates and products in the enzyme cavity, suggesting in particular that basic substrates interact with the enzyme in their unprotonated form.
(PMID: 19932971)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Categorized Comment
Assay Type: Binding

Assay Data Source: Scientific Literature

Assay Test Type: In vitro

BAO: Assay Format: cell-based format

Target Type: Target is a single protein chain

Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Km*Km PubChem standard valueFloatμM
2Km activity commentKm activity commentString
3Km standard flagKm standard flagInteger
4Km qualifierKm qualifierString
5Km published valueKm published valueFloatμM
6Km standard valueKm standard valueFloatnM
7pKm activity commentpKm activity commentString
8pKm standard flagpKm standard flagInteger
9pKm qualifierpKm qualifierString
10pKm published valuepKm published valueFloat
11pKm standard valuepKm standard valueFloat

* Activity Concentration.

Data Table (Concise)
Data Table ( Complete ):     View Active Data    View All Data
Classification
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