Modulation of phosphofructokinase (PFK) from <it>Setaria cervi</it>, a bovine filarial parasite, by different effectors and its interaction with some antifilarials
<p>Abstract</p> <p>Background</p> <p>Phosphofructokinase (ATP: D-fructose-6-phosphate-1-phosphotransferase, EC 2.7.1.11, PFK) is of primary importance in the regulation of glycolytic flux. This enzyme has been extensively studied from mammalian sources but relatively le...
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| Format: | Article |
| Language: | English |
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BMC
2011-12-01
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| Series: | Parasites & Vectors |
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| Online Access: | http://www.parasitesandvectors.com/content/4/1/227 |
| _version_ | 1828219449618989056 |
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| author | Sharma Bechan |
| author_facet | Sharma Bechan |
| author_sort | Sharma Bechan |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Phosphofructokinase (ATP: D-fructose-6-phosphate-1-phosphotransferase, EC 2.7.1.11, PFK) is of primary importance in the regulation of glycolytic flux. This enzyme has been extensively studied from mammalian sources but relatively less attention has been paid towards its characterization from filarial parasites. Furthermore, the information about the response of filarial PFK towards the anthelmintics/antifilarial compounds is lacking. In view of these facts, PFK from <it>Setaria cervi</it>, a bovine filarial parasite having similarity with that of human filarial worms, was isolated, purified and characterized.</p> <p>Results</p> <p>The <it>S. cervi </it>PFK was cytosolic in nature. The adult parasites (both female and male) contained more enzyme activity than the microfilarial (Mf) stage of <it>S. cervi</it>, which exhibited only 20% of total activity. The <it>S. cervi </it>PFK could be modulated by different nucleotides and the response of enzyme to these nucleotides was dependent on the concentrations of substrates (F-6-P and ATP). The enzyme possessed wide specificity towards utilization of the nucleotides as phosphate group donors. <it>S. cervi </it>PFK showed the presence of thiol group(s) at the active site of the enzyme, which could be protected from inhibitory action of para-chloromercuribenzoate (p-CMB) up to about 76% by pretreatment with cysteine or β-ME. The sensitivity of PFK from <it>S. cervi </it>towards antifilarials/anthelmintics was comparatively higher than that of mammalian PFK. With suramin, the Ki value for rat liver PFK was 40 times higher than PFK from <it>S. cervi</it>.</p> <p>Conclusions</p> <p>The results indicate that the activity of filarial PFK may be modified by different effectors (such as nucleotides, thiol group reactants and anthelmintics) in filarial worms depending on the presence of varying concentrations of substrates (F-6-P and ATP) in the cellular milieu. It may possess thiol group at its active site responsible for catalysis. Relatively, 40 times higher sensitivity of filarial PFK towards suramin as compared to the analogous enzyme from the mammalian system indicates that this enzyme could be exploited as a potential chemotherapeutic target against filariasis.</p> |
| first_indexed | 2024-04-12T16:15:49Z |
| format | Article |
| id | doaj.art-d509300372004afcae9fe3a4d2c03962 |
| institution | Directory Open Access Journal |
| issn | 1756-3305 |
| language | English |
| last_indexed | 2024-04-12T16:15:49Z |
| publishDate | 2011-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Parasites & Vectors |
| spelling | doaj.art-d509300372004afcae9fe3a4d2c039622022-12-22T03:25:43ZengBMCParasites & Vectors1756-33052011-12-014122710.1186/1756-3305-4-227Modulation of phosphofructokinase (PFK) from <it>Setaria cervi</it>, a bovine filarial parasite, by different effectors and its interaction with some antifilarialsSharma Bechan<p>Abstract</p> <p>Background</p> <p>Phosphofructokinase (ATP: D-fructose-6-phosphate-1-phosphotransferase, EC 2.7.1.11, PFK) is of primary importance in the regulation of glycolytic flux. This enzyme has been extensively studied from mammalian sources but relatively less attention has been paid towards its characterization from filarial parasites. Furthermore, the information about the response of filarial PFK towards the anthelmintics/antifilarial compounds is lacking. In view of these facts, PFK from <it>Setaria cervi</it>, a bovine filarial parasite having similarity with that of human filarial worms, was isolated, purified and characterized.</p> <p>Results</p> <p>The <it>S. cervi </it>PFK was cytosolic in nature. The adult parasites (both female and male) contained more enzyme activity than the microfilarial (Mf) stage of <it>S. cervi</it>, which exhibited only 20% of total activity. The <it>S. cervi </it>PFK could be modulated by different nucleotides and the response of enzyme to these nucleotides was dependent on the concentrations of substrates (F-6-P and ATP). The enzyme possessed wide specificity towards utilization of the nucleotides as phosphate group donors. <it>S. cervi </it>PFK showed the presence of thiol group(s) at the active site of the enzyme, which could be protected from inhibitory action of para-chloromercuribenzoate (p-CMB) up to about 76% by pretreatment with cysteine or β-ME. The sensitivity of PFK from <it>S. cervi </it>towards antifilarials/anthelmintics was comparatively higher than that of mammalian PFK. With suramin, the Ki value for rat liver PFK was 40 times higher than PFK from <it>S. cervi</it>.</p> <p>Conclusions</p> <p>The results indicate that the activity of filarial PFK may be modified by different effectors (such as nucleotides, thiol group reactants and anthelmintics) in filarial worms depending on the presence of varying concentrations of substrates (F-6-P and ATP) in the cellular milieu. It may possess thiol group at its active site responsible for catalysis. Relatively, 40 times higher sensitivity of filarial PFK towards suramin as compared to the analogous enzyme from the mammalian system indicates that this enzyme could be exploited as a potential chemotherapeutic target against filariasis.</p>http://www.parasitesandvectors.com/content/4/1/227Phosphofructokinase<it>Setaria cervi</it>NucleotidesSpecificityActivationInhibitionAntifilarials |
| spellingShingle | Sharma Bechan Modulation of phosphofructokinase (PFK) from <it>Setaria cervi</it>, a bovine filarial parasite, by different effectors and its interaction with some antifilarials Parasites & Vectors Phosphofructokinase <it>Setaria cervi</it> Nucleotides Specificity Activation Inhibition Antifilarials |
| title | Modulation of phosphofructokinase (PFK) from <it>Setaria cervi</it>, a bovine filarial parasite, by different effectors and its interaction with some antifilarials |
| title_full | Modulation of phosphofructokinase (PFK) from <it>Setaria cervi</it>, a bovine filarial parasite, by different effectors and its interaction with some antifilarials |
| title_fullStr | Modulation of phosphofructokinase (PFK) from <it>Setaria cervi</it>, a bovine filarial parasite, by different effectors and its interaction with some antifilarials |
| title_full_unstemmed | Modulation of phosphofructokinase (PFK) from <it>Setaria cervi</it>, a bovine filarial parasite, by different effectors and its interaction with some antifilarials |
| title_short | Modulation of phosphofructokinase (PFK) from <it>Setaria cervi</it>, a bovine filarial parasite, by different effectors and its interaction with some antifilarials |
| title_sort | modulation of phosphofructokinase pfk from it setaria cervi it a bovine filarial parasite by different effectors and its interaction with some antifilarials |
| topic | Phosphofructokinase <it>Setaria cervi</it> Nucleotides Specificity Activation Inhibition Antifilarials |
| url | http://www.parasitesandvectors.com/content/4/1/227 |
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