Transmembrane proteins of Fasciola hepatica: identification and characterization of new putative drug targets

2015 ◽  
Vol 3 (Suppl. 2) ◽  
pp. A3.3
Author(s):  
Bulut Hamali
Keyword(s):  
Drug Targets ◽  
Fasciola Hepatica ◽  
Transmembrane Proteins ◽  
Identification And Characterization

scholarly journals A small mitochondrial protein present in myzozoans is essential for malaria transmission

Open Biology ◽  
2016 ◽  
Vol 6 (4) ◽  
pp. 160034 ◽  
Author(s):  
Dennis Klug ◽  
Gunnar R. Mair ◽  
Friedrich Frischknecht ◽  
Ross G. Douglas
Keyword(s):  
Drug Targets ◽  
Mitochondrial Protein ◽  
Sister Group ◽  
Developmental Defect ◽  
Mitochondrial Mass ◽  
First Time ◽  
Potential Drug Targets ◽  
Identification And Characterization

Myzozoans (which include dinoflagellates, chromerids and apicomplexans) display notable divergence from their ciliate sister group, including a reduced mitochondrial genome and divergent metabolic processes. The factors contributing to these divergent processes are still poorly understood and could serve as potential drug targets in disease-causing protists. Here, we report the identification and characterization of a small mitochondrial protein from the rodent-infecting apicomplexan parasite Plasmodium berghei that is essential for development in its mosquito host. Parasites lacking the gene mitochondrial protein ookinete developmental defect ( mpodd ) showed malformed parasites that were unable to transmit to mosquitoes. Knockout parasites displayed reduced mitochondrial mass without affecting organelle integrity, indicating no role of the protein in mitochondrial biogenesis or morphology maintenance but a likely role in mitochondrial import or metabolism. Using genetic complementation experiments, we identified a previously unrecognized Plasmodium falciparum homologue that can rescue the mpodd(−) phenotype, thereby showing that the gene is functionally conserved. As far as can be detected, mpodd is found in myzozoans, has homologues in the phylum Apicomplexa and appears to have arisen in free-living dinoflagellates. This suggests that the MPODD protein has a conserved mitochondrial role that is important for myzozoans. While previous studies identified a number of essential proteins which are generally highly conserved evolutionarily, our study identifies, for the first time, a non-canonical protein fulfilling a crucial function in the mitochondrion during parasite transmission.

scholarly journals Identification and characterization of the STIM (stromal interaction molecule) gene family: coding for a novel class of transmembrane proteins

2001 ◽  
Vol 357 (3) ◽  
pp. 673 ◽  
Author(s):  
Richard T. WILLIAMS ◽  
Shehnaaz S. M. MANJI ◽  
Nigel J. PARKER ◽  
Manuela S. HANCOCK ◽  
Leonie VAN STEKELENBURG ◽  
...  
Keyword(s):  
Gene Family ◽  
Transmembrane Proteins ◽  
Identification And Characterization

scholarly journals Identification and characterization of the Fasciola hepatica sodium- and chloride-dependent taurine transporter

2018 ◽  
Vol 12 (4) ◽  
pp. e0006428
Author(s):  
Bulut Hamali ◽  
Sandra Pichler ◽  
Elisabeth Wischnitzki ◽  
Klaus Schicker ◽  
Melanie Burger ◽  
...  
Keyword(s):  
Fasciola Hepatica ◽  
Taurine Transporter ◽  
Identification And Characterization

Biosensor-Based Screening and Characterization of HIV-1 Inhibitor Interactions with Sap 1, Sap 2, and Sap 3 from Candida albicans

2005 ◽  
Vol 11 (2) ◽  
pp. 165-175 ◽  
Author(s):  
Dan Backman ◽  
Michel Monod ◽  
U. Helena Danielson
Keyword(s):  
Candida Albicans ◽  
Drug Targets ◽  
Ph Dependence ◽  
Interaction Mechanism ◽  
Inhibitory Effect ◽  
Lead Compounds ◽  
Small Set ◽  
Identification And Characterization ◽  
Hiv 1

A surface plasmon resonance (SPR) biosensor-based strategy for identification and characterization of compounds has been devised as a tool for the discovery of specific drugs for treatment of Candida albicans infections. Three secreted aspartic pro-teases (Saps 1-3) from C. albicans were used as parallel targets. The stepwise procedure involved screening of 104 HIV-1 pro-tease inhibitors at a single concentration for binding to the targets. Twenty-four compounds that appeared to interact with the targets were identified in the screen. False positives and compounds with low affinities or very fast dissociation rates could be removed after a series of additional measurements of these compounds at 3 different concentrations. Kinetic characterization was performed with 13 compounds, giving information about the interaction mechanism and interaction kinetic parameters (kon, koff, andKD). The pH dependence of the interaction and the inhibitory effect of a final small set of compounds were also evaluated. The strategy resulted in the identification of ritonavir as the compound generally exhibiting the highest affinity for the Candida enzymes. It had similar interaction kinetic characteristics for Sap 1 and Sap 2 but a lower affinity for Sap 3 due to a slower association rate. Several additional compounds with high affinity and/or slow dissociation rates for the targets were identified, revealing 2 other structural scaffolds for Sap inhibitors. In addition, important differences in the specificity for these types of compounds by the Saps were identified. The stepwise biosensor-based strategy was consequently efficient for identification and characterization of new lead compounds for 3 important drug targets.

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