Trypanosoma cruzi calmodulin: Cloning, expression and characterization

García-Marchán, Yael; Sojo, Felipe; Rodriguez, Evelyn J.; Zerpa, Noraida; Malavé, Caridad; Galindo-Castro, Iván; Salerno, Milena; Benaím, Gustavo

doi:10.1016/j.exppara.2009.08.010

Cited by 7 publications

(6 citation statements)

References 33 publications

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“…However, albeit possessing the same molecular mass as the vertebrate CaM, T. cruzi CaM migrates more to the anode (lower apparent molecular mass), likely due to its more hydrophobic character. This is concordant with circular dichroism studies, which have confirmed that in the presence of Ca 2+ the α-helix content of T. cruzi CaM is increased is comparison to mammal CaM (Garcia-Marchan et al, 2009).…”

Section: Intracellular Ca 2+ Regulation In Human Cells and Critical Dsupporting

confidence: 91%

“…Vertebrate CaM is characterized by a Ca 2+ -shift when run on SDS-PAGE in the presence or absence of the calcium chelator EGTA (i.e., with or without Ca 2+ ). This trademark of CaM is probably due to the increase in the α-helix content and the concomitantly increase in the hydrophobic character of the protein, or the acquisition of a more globular shape, even in the presence of SDS (Garcia-Marchan et al, 2009). Similarly, a Ca 2+ -shift also has been observed in T. cruzi CaM.…”

Section: Intracellular Ca 2+ Regulation In Human Cells and Critical Dmentioning

confidence: 91%

“…As mentioned, CaM is able to stimulate the T. cruzi PMCA; the affinity of the human PMCA for CaM is slightly lower than for T. cruzi CaM. In addition, the CaM-anatgonists trifluoperazine and calmidazolium, have been shown to have less inhibitory activity when the PMCA is stimulated by the T. cruzi CaM when compared to rat CaM (Garcia-Marchan et al, 2009). These findings raise the possibility that there is a still-undiscovered CaM target in this parasite that could reflect the prominent differences in structure encountered between the T. cruzi and vertebrate proteins.…”

Section: Intracellular Ca 2+ Regulation In Human Cells and Critical Dmentioning

confidence: 95%

“…The differences between human and T. cruzi CaM deserve special consideration, given that this ubiquitous Ca 2+ binding protein has been highly-conserved in eukaryotes, with trypanosomatids being a remarkable exception. Although vertebrate and trypanosomatid CaMs all have 148 amino acids, and the structure of CaM is identical in all vertebrates, there are 16 amino acid substitutions between T. cruzi CaM when compared to vertebrate CaM (∼89 % homology) (Garcia-Marchan et al, 2009). Trypanosomes contain three genes tandemly repeated for CaM, and this protein is highly expressed in these parasites (Chung and Swindel, 1990).…”

Section: Intracellular Ca 2+ Regulation In Human Cells and Critical Dmentioning

confidence: 99%

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Disruption of Intracellular Calcium Homeostasis as a Therapeutic Target Against Trypanosoma cruzi

Benaím

Paniz‐Mondolfi

Sordillo

et al. 2020

Front. Cell. Infect. Microbiol.

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There is no effective cure for Chagas disease, which is caused by infection with the arthropod-borne parasite, Trypanosoma cruzi. In the search for new drugs to treat Chagas disease, potential therapeutic targets have been identified by exploiting the differences between the mechanisms involved in intracellular Ca 2+ homeostasis, both in humans and in trypanosomatids. In the trypanosomatid, intracellular Ca 2+ regulation requires the concerted action of three intracellular organelles, the endoplasmic reticulum, the single unique mitochondrion, and the acidocalcisomes. The single unique mitochondrion and the acidocalcisomes also play central roles in parasite bioenergetics. At the parasite plasma membrane, a Ca 2+-− ATPase (PMCA) with significant differences from its human counterpart is responsible for Ca 2+ extrusion; a distinctive sphingosine-activated Ca 2+ channel controls Ca 2+ entrance to the parasite interior. Several potential anti-trypansosomatid drugs have been demonstrated to modulate one or more of these mechanisms for Ca 2+ regulation. The antiarrhythmic agent amiodarone and its derivatives have been shown to exert trypanocidal effects through the disruption of parasite Ca 2+ homeostasis. Similarly, the amiodarone-derivative dronedarone disrupts Ca 2+ homeostasis in T. cruzi epimastigotes, collapsing the mitochondrial membrane potential (Ψ m), and inducing a large increase in the intracellular Ca 2+ concentration ([Ca 2+ ] i) from this organelle and from the acidocalcisomes in the parasite cytoplasm. The same general mechanism has been demonstrated for SQ109, a new anti-tuberculosis drug with potent trypanocidal effect. Miltefosine similarly induces a large increase in the [Ca 2+ ] i acting on the sphingosine-activated Ca 2+ channel, the mitochondrion and acidocalcisomes. These examples, in conjunction with other evidence we review herein, strongly support targeting Ca 2+ homeostasis as a strategy against Chagas disease.

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Section: Intracellular Ca 2+ Regulation In Human Cells and Critical Dsupporting

confidence: 91%

Section: Intracellular Ca 2+ Regulation In Human Cells and Critical Dmentioning

confidence: 91%

Section: Intracellular Ca 2+ Regulation In Human Cells and Critical Dmentioning

confidence: 95%

Section: Intracellular Ca 2+ Regulation In Human Cells and Critical Dmentioning

confidence: 99%

See 2 more Smart Citations

Disruption of Intracellular Calcium Homeostasis as a Therapeutic Target Against Trypanosoma cruzi

Benaím

Paniz‐Mondolfi

Sordillo

et al. 2020

Front. Cell. Infect. Microbiol.

Self Cite

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“…Ebselen ( 5 ) is an organoselenium compound reported as cysteine oxidant or modifier 58–60 that inhibits Tri-Tryp TryS within a narrow range of concentrations (IC 50 = 3–14 µM). Despite Ebselen may show some promiscuity for modifying thiol groups, not all cysteine residues are capable to react and generate stable complexes with it.…”

Section: Discussionmentioning

confidence: 99%

Drug-like molecules with anti-trypanothione synthetase activity identified by high throughput screening

Benítez

Franco

Sardi

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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Identification, Molecular and Functional Characterization of Calmodulin Gene of Phytomonas serpens 15T that Shares High Similarity with its Pathogenic Counterparts Trypanosoma cruzi

Souza

Lancheros

et al. 2011

Protein J

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In trypanosomatids, Ca²+-binding proteins can affect parasite growth, differentiation and invasion. Due to their importance for parasite maintenance, they become an attractive target for drug discovery and design. Phytomonas serpens 15T is a non-human pathogenic trypanosomatid that expresses important protein homologs of human pathogenic trypanosomatids. In this study, the coding sequence of calmodulin, a Ca²+-binding protein, of P. serpens 15T was cloned and characterized. The encoded polypeptide (CaMP) displayed high amino acid identity to homolog protein of Trypanosoma cruzi and four helix-loop-helix motifs were found. CaMP sequence analysis showed 20 amino acid substitutions compared to its mammalian counterparts. This gene is located on a chromosomal band with estimated size of 1,300 kb and two transcripts were detected by Northern blot analysis. A polyclonal antiserum raised against the recombinant protein recognized a polypeptide with an estimated size of 17 kDa in log-phase promastigote extracts. The recombinant CaMP retains its Ca²+-binding capacity.

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Trypanosoma cruzi calmodulin: Cloning, expression and characterization

Cited by 7 publications

References 33 publications

Disruption of Intracellular Calcium Homeostasis as a Therapeutic Target Against Trypanosoma cruzi

Disruption of Intracellular Calcium Homeostasis as a Therapeutic Target Against Trypanosoma cruzi

Drug-like molecules with anti-trypanothione synthetase activity identified by high throughput screening

Identification, Molecular and Functional Characterization of Calmodulin Gene of Phytomonas serpens 15T that Shares High Similarity with its Pathogenic Counterparts Trypanosoma cruzi

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