@article {44655,
	title = {Highly diverged novel subunit composition of apicomplexan F-type ATP synthase identified from Toxoplasma gondii},
	journal = {Plos Biology},
	volume = {16},
	year = {2018},
	month = {JUL},
	pages = {e2006128},
	type = {Article},
	abstract = {<p>The mitochondrial F-type ATP synthase, a multisubunit nanomotor, is critical for maintaining cellular ATP levels. In T. gondii and other apicomplexan parasites, many subunit components necessary for proper assembly and functioning of this enzyme appear to be missing. Here, we report the identification of 20 novel subunits of T. gondii F-type ATP synthase from mass spectrometry analysis of partially purified monomeric (approximately 600 kDa) and dimeric (\&gt; 1 MDa) forms of the enzyme. Despite extreme sequence diversification, key F-O subunits a, b, and d can be identified from conserved structural features. Orthologs for these proteins are restricted to apicomplexan, chromerid, and dinoflagellate species. Interestingly, their absence in ciliates indicates a major diversion, with respect to subunit composition of this enzyme, within the alveolate clade. Discovery of these highly diversified novel components of the apicomplexan F-type ATP synthase complex could facilitate the development of novel antiparasitic agents. Structural and functional characterization of this unusual enzyme complex will advance our fundamental understanding of energy metabolism in apicomplexan species.</p>},
	issn = {1545-7885},
	doi = {10.1371/journal.pbio.2006128},
	author = {Salunke, Rahul and Mourier, Tobias and Banerjee, Manidipa and Pain, Arnab and Shanmugam, Dhanasekaran}
}
@article {48323,
	title = {Histidinal-based potent antimalarial agents},
	journal = {ChemMedChem},
	volume = {18},
	year = {2023},
	month = {MAY },
	type = {Article},
	abstract = {<p>
	Herein we report the synthesis and evaluation of peptide-histidinal conjugated drug scaffolds, which have the potential to target the hemoglobin-degrading proteases falcipain-2/3 from the human malaria parasite. Scaffolds with various substitutions were tested for antimalarial activity, and compounds 8 g, 8 h, and 15 exhibited EC50 values of similar to 0.018 mu M, similar to 0.069 mu M, and similar to 0.02 mu M, respectively. Structure-based docking studies on falcipain-2/3 proteases (PDB:2GHU and PDB:3BWK) revealed that compounds 8 g, 8 h, and 15 interact strongly with binding sites of falcipain-2/3 in a substrate-like manner. In silico ADME studies revealed that the molecules of interest showed no or minimal violations of drug-likeness parameters. Further, phenotypic assays revealed that compound 8 g and its biotinylated version inhibit hemoglobin degradation in the parasite food vacuole. The identification of falcipain-2/3 targeting potent inhibitors of the malaria parasite can serve as a starting point for the development of lead compounds as future antimalarial drug candidates.</p>
},
	keywords = {artemisinin, chloroquine, digestive vacuole, docking, falcipains, falciparum, P},
	issn = {1860-7179},
	doi = {10.1002/cmdc.202200709},
	author = {Meena, Chhuttan L. and Hingamire, Tejashri and Gupta, Tanya and Deshmukh, Bhagyashree and Karmodiya, Krishanpal and Joshi, Rakesh and Shanmugam, Dhanasekaran and Sanjayan, Gangadhar J.}
}
