Bookmark and Share
BioAssay: AID 552785

Inhibition of Streptococcus pneumoniae beta-carbonic anhydrase after 15 mins by stopped flow CO2 hydration assay

The Gram-positive bacterium Streptococcus pneumoniae is a human respiratory tract pathogen that contributes significantly to global mortality and morbidity. It was recently shown that this bacterial pathogen depends on a conserved beta-carbonic anhydrase (CA, EC 4.2.1.1) for in vitro growth in environmental ambient air and during intracellular survival in host cells. Hence, it is to be expected more ..
_
   
 Tested Compounds
 Tested Compounds
All(31)
 
 
Active(15)
 
 
Unspecified(16)
 
 
 Tested Substances
 Tested Substances
All(34)
 
 
Active(16)
 
 
Unspecified(18)
 
 
 Related BioAssays
 Related BioAssays
AID: 552785
Data Source: ChEMBL (701313)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2011-09-18
Modify Date: 2014-05-26

Data Table ( Complete ):           View Active Data    View All Data
BioActive Compounds: 15
Description:
Title: Inhibition of the beta-carbonic anhydrase from Streptococcus pneumoniae by inorganic anions and small molecules: Toward innovative drug design of antiinfectives?

Abstract: The Gram-positive bacterium Streptococcus pneumoniae is a human respiratory tract pathogen that contributes significantly to global mortality and morbidity. It was recently shown that this bacterial pathogen depends on a conserved beta-carbonic anhydrase (CA, EC 4.2.1.1) for in vitro growth in environmental ambient air and during intracellular survival in host cells. Hence, it is to be expected that this pneumococcal carbonic anhydrase (PCA) contributes to transmission and pathogenesis of the bacterium, making it a potential therapeutic target. In this study, purified recombinant PCA has been further characterized kinetically and for inhibition with a series of inorganic anions and small molecules useful as leads. PCA has appreciable activity as catalyst for the hydration of CO(2) to bicarbonate, with a k(cat) of 7.4#10(5)s(-1) and k(cat)/K(m) of 6.5#10(7) M(-1)s(-1) at an optimum pH of 8.4. Inorganic anions such as chloride, bromide, iodide, cyanate, selenocyanate, trithiocarbonate, and cyanide were effective inhibitors of PCA (K(I)s of 21-98muM). Sulfamide, sulfamic acid, phenylboronic, phenylarsonic acid, and diethyldithiocarbamate showed inhibition constants in the low micromolar/submicromolar range (K(I)s of 0.61-6.68muM), whereas that of the sulfonamide acetazolamide was in the nanomolar range (K(I)s 89nM). In conclusion, our results show that PCA can effectively be inhibited by a range of molecules that could be interesting leads for obtaining more potent PCA inhibitors. PCA might be a novel target for designing antimicrobial drugs with a new mechanism of action.
(PMID: 21163660)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.
Putative Target:
ChEMBL Target ID: 22226
Target Type: UNCHECKED
Pref Name: Unchecked
Confidence: Default value - Target unknown or has yet to be assigned
Relationship Type: Default value - Target has yet to be curated
Categorized Comment - additional comments and annotations
From ChEMBL:
Assay Type: Binding
Assay Data Source: Scientific Literature
Result Definitions
Show more
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Ki*Ki PubChem standard valueFloatμM
2Ki activity commentKi activity commentString
3Ki standard flagKi standard flagInteger
4Ki qualifierKi qualifierString
5Ki published valueKi published valueFloatmM
6Ki standard valueKi standard valueFloatnM
7Ki data validityKi data validityString
8Ki activity commentKi activity commentString
9Ki standard flagKi standard flagInteger
10Ki qualifierKi qualifierString
11Ki published valueKi published valueFloatμM
12Ki standard valueKi standard valueFloatnM
13Ki data validityKi data validityString

* Activity Concentration.

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