Please use this identifier to cite or link to this item: http://nopr.niscair.res.in/handle/123456789/4374
Title: A novel calcium binding protein in <i style="">Mycobacterium tuberculosis</i>—Potential target for trifluoperazine
Authors: Koul, Sunaina
Somayajulu, Aruna
Advani, Meeta J
Reddy, Hemalatha
Keywords: Calcium binding protein
Calmodulin
<i style="">Mycobacterium tuberculosis</i>
NAD-kinase
Nickel affinity column
Trifluoperazine
Issue Date: Jun-2009
Publisher: CSIR
Abstract: Phenothiazines have been reported for anti-mycobacterial activity by inhibiting calcium binding proteins, potassium transport processes of phagolysosomes, NADH dependent oxygen consumption by <i>M. tuberculosis</i> membranes and DNA, and lipid synthesis of the bacterium. Thioridazine (TZ), chloropromazine (CPZ) and trifluoperazine (TFP) belong to the class of phenothiazines widely used as neuroleptic drugs. Trifluoperazine, a calmodulin antagonist in eukaryotes, binds to a similar protein containing prototypical EF hand to bind to calcium in <i>M. tubercu</i><i style="">losis</i>. Calmodulin, a calcium binding protein, plays a critical role in regulating the activities of several enzymes in response to intracellular calcium levels. Since calmodulins are best characterized in eukaryotes as opposed to prokaryotes, the presence of calmodulin-like activity in <i style="">M. tuberculosis</i>, the causative agent of tuberculosis, is unknown. We have provided biochemical evidence that <i>M. tuberculosis</i> recombinant (r) Rv1211 gene product stimulates the activities of heterologous calcium-deficient NAD-kinase and bovine brain phosphodiesterase (PDE), much like the eukaryotic calmodulins. Further we have shown that EGTA, a calcium chelator, inhibits rRv1211-stimulated NAD-kinase and PDE activities. We have also shown that trifluoperazine interferes with the activation of NAD-kinase and PDE activities by Rv1211. Using a bioinformatics approach, we have shown that Rv1211 contains one prototypical calcium-binding EF-hand motif, a characteristic feature of calmodulins. Based on these data, we conclude that Rv1211 encodes a protein with calmodulin-like activity (CAMLP) in the human pathogen <i>M. tuberculosis </i>and acts as a potential target for trifluoperazine<i>. </i>
Description: 480-488
URI: http://hdl.handle.net/123456789/4374
ISSN: 0019-5189
Appears in Collections:IJEB Vol.47(06) [June 2009]

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