A Structural Bioinformatics Study of Calcium Dependent Protein Kinase 6 (CDPK6) of Cryptosporidium Parvum for Identification of Novel Therapeutics

2020 ◽  
Author(s):  
Ajit Kumar Dhal ◽  
Subhashree Rout ◽  
Rajani Kanta Mahapatra
Keyword(s):  
Protein Kinase ◽  
Cryptosporidium Parvum ◽  
Structural Bioinformatics ◽  
Dependent Protein Kinase ◽  
Novel Therapeutics ◽  
Calcium Dependent ◽  
Dependent Protein ◽  
Bioinformatics Study ◽  
Calcium Dependent Protein Kinase

scholarly journals Inhibition of Calcium-Dependent Protein Kinase 1 (CDPK1)In Vitroby Pyrazolopyrimidine Derivatives Does Not Correlate with Sensitivity of Cryptosporidium parvum Growth in Cell Culture

2015 ◽  
Vol 60 (1) ◽  
pp. 570-579 ◽  
Author(s):  
Theresa B. Kuhlenschmidt ◽  
Florentine U. Rutaganira ◽  
Shaojun Long ◽  
Keliang Tang ◽  
Kevan M. Shokat ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cryptosporidium Parvum ◽  
Cell Invasion ◽  
Parasite Growth ◽  
Dependent Protein Kinase ◽  
Content Type ◽  
Calcium Dependent ◽  
Dependent Protein ◽  
Calcium Dependent Protein Kinase

ABSTRACTCryptosporidiosis is a serious diarrheal disease in immunocompromised patients and malnourished children, and treatment is complicated by a lack of adequate drugs. Recent studies suggest that the natural occurrence of a small gatekeeper residue in serine threonine calcium-dependent protein kinase 1 (CDPK1) ofCryptosporidium parvummight be exploited to target this enzyme and block parasite growth. Here were explored the potency with which a series of pyrazolopyrimidine analogs, which are selective for small gatekeeper kinases, inhibitC. parvumCDPK1 and blockC. parvumgrowth in tissue culturein vitro. Although these compounds potently inhibited kinase activityin vitro, most had no effect on parasite growth. Moreover, among those that were active against parasite growth, there was a very poor correlation with their 50% inhibitory concentrations against the enzyme. Active compounds also had no effect on cell invasion, unlike the situation inToxoplasma gondii, where these compounds block CDPK1, prevent microneme secretion, and disrupt cell invasion. These findings suggest that CPDK1 is not essential forC. parvumhost cell invasion or growth and therefore that it is not the optimal target for therapeutic intervention. Nonetheless, several inhibitors with low micromolar 50% effective concentrations were identified, and these may affect other essential targets inC. parvumthat are worthy of further exploration.

scholarly journals A Novel Calcium-Dependent Protein Kinase 1 Inhibitor Potently Prevents Toxoplasma gondii Transmission to Foetuses in Mouse

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4203
Author(s):  
Héloïse Débare ◽  
Nathalie Moiré ◽  
Firmin Baron ◽  
Louis Lantier ◽  
Bruno Héraut ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Toxoplasma Gondii ◽  
Intraperitoneal Administration ◽  
Congenital Toxoplasmosis ◽  
Parasite Burden ◽  
Oral Route ◽  
Dependent Protein Kinase ◽  
Calcium Dependent ◽  
Dependent Protein ◽  
Calcium Dependent Protein Kinase

Treatments currently used to prevent congenital toxoplasmosis are non-specific of Toxoplasma gondii and have grievous side effects. To develop a more specific and less toxic drug, we have designed SP230, an imidazo[1,2-b]pyridazine salt targeting the Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) and active against acute toxoplasmosis in mice. Efficiency of SP230 to inhibit foetal transmission of the parasite was evaluated in a mouse model of congenital toxoplasmosis. Swiss mice were infected at mid-pregnancy with tachyzoites or cysts of the ME49 strain of T. gondii by intraperitoneal and oral route, respectively, and treated with SP230 at 50 mg/kg for 5 days by the same routes. Parasite burden in organs of dams and in foetuses was measured by quantitative PCR. Intraperitoneal administration of SP230 drastically reduced the number of parasites (more than 97% of reduction) in the brain and lungs of dams, and led to a reduction of 66% of parasite burden in foetuses. Oral administration of SP230 was particularly efficient with 97% of reduction of parasite burdens in foetuses. SP230 did not impact number and weight of offspring in our conditions. This inhibitor of TgCDPK1 is a promising candidate for the development of alternative therapeutics to treat infected pregnant women.

scholarly journals The Evolutionary History and Diverse Physiological Roles of the Grapevine Calcium-Dependent Protein Kinase Gene Family

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e80818 ◽  
Author(s):  
Fei Chen ◽  
Marianna Fasoli ◽  
Giovanni Battista Tornielli ◽  
Silvia Dal Santo ◽  
Mario Pezzotti ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Gene Family ◽  
Evolutionary History ◽  
Dependent Protein Kinase ◽  
Kinase Gene ◽  
Calcium Dependent ◽  
Dependent Protein ◽  
Protein Kinase Gene ◽  
Calcium Dependent Protein Kinase

scholarly journals Genome-wide identification and expression analysis of calcium-dependent protein kinase in maize

BMC Genomics ◽  
2013 ◽  
Vol 14 (1) ◽  
pp. 433 ◽  
Author(s):  
Xiangpei Kong ◽  
Wei Lv ◽  
Shanshan Jiang ◽  
Dan Zhang ◽  
Guohua Cai ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Expression Analysis ◽  
Dependent Protein Kinase ◽  
Calcium Dependent ◽  
Genome Wide ◽  
Dependent Protein ◽  
Calcium Dependent Protein Kinase
Sign in / Sign up

Export Citation Format

Share Document