@article { ISI:000361402900006,
	title = {Cathepsins of lepidopteran insects: aspects and prospects},
	journal = {Insect Biochemistry and Molecular Biology},
	volume = {64},
	year = {2015},
	month = {SEP},
	pages = {51-59},
	publisher = {PERGAMON-ELSEVIER SCIENCE LTD},
	address = {THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND},
	abstract = {<p>Molecular understanding of lepidopteran physiology has revealed that proteases consist of one of the central regulatory/reacting system for insect growth and survival. Among the various proteases, cathepsins are the most crucial cellular proteases, which play vital roles during insect development. In the present review, we have discussed various aspects of the lepidopteran insect cathepsins, emphasizing their roles in processes like development, growth, metamorphosis, apoptosis and immunity. Cathepsins are categorized into different types on the basis of their sequence diversification, leading to variation in structure and catalytic function. Cathepsins exhibit tissue and stage specific expression pattern which is fine-tuned by a delicate balance of expression, compartmentalization, zymogen activation, inhibition by protein inhibitors and degradation. The indispensability of cathepsins as cellular proteases in the above mentioned processes proposes them as novel targets for designing effective and specific insect controlling strategies. (C) 2015 Elsevier Ltd. All rights reserved.</p>},
	keywords = {Apoptosis, Cathepsin, Cysteine/aspartate protease, Development, Lepidoptera, Pest control, Stress response},
	issn = {0965-1748},
	doi = {10.1016/j.ibmb.2015.07.005},
	author = {Saikhedkar, Nidhi and Summanwar, Aarohi and Joshi, Rakesh S. and Giri, Ashok P.}
}
@article {47126,
	title = {Repurposing the McoTI-II rigid molecular scaffold in to inhibitor of {\textquoteleft}papain superfamily{\textquoteright} cysteine proteases},
	journal = {Pharmaceuticals},
	volume = {14},
	year = {2021},
	month = {JAN},
	pages = {7},
	type = {Article},
	abstract = {<p>Clan C1A or {\textquoteleft}papain superfamily{\textquoteright} cysteine proteases are key players in many important physiological processes and diseases in most living systems. Novel approaches towards the development of their inhibitors can open new avenues in translational medicine. Here, we report a novel design of a re-engineered chimera inhibitor Mco-cysteine protease inhibitor (CPI) to inhibit the activity of C1A cysteine proteases. This was accomplished by grafting the cystatin first hairpin loop conserved motif (QVVAG) onto loop 1 of the ultrastable cyclic peptide scaffold McoTI-II. The recombinantly expressed Mco-CPI protein was able to bind with micromolar affinity to papain and showed remarkable thermostability owing to the formation of multi-disulphide bonds. Using an in silico approach based on homology modelling, protein-protein docking, the calculation of the free-energy of binding, the mechanism of inhibition of Mco-CPI against representative C1A cysteine proteases (papain and cathepsin L) was validated. Furthermore, molecular dynamics simulation of the Mco-CPI-papain complex validated the interaction as stable. To conclude, in this McoTI-II analogue, the specificity had been successfully redirected towards C1A cysteine proteases while retaining the moderate affinity. The outcomes of this study pave the way for further modifications of the Mco-CPI design for realizing its full potential in therapeutics. This study also demonstrates the relevance of ultrastable peptide-based scaffolds for the development of novel inhibitors via grafting.</p>
},
	keywords = {Cathepsin, Clan CA cysteine proteases, cyclotide, cystatin, McoTI-II, papain, protein engineering},
	doi = {10.3390/ph14010007},
	author = {Mishra, Manasi and Singh, Vigyasa and Tellis, Meenakshi B. and Joshi, Rakesh S. and Singh, Shailja}
}
