01985nas a2200265   4500008004100000022001400041245006200055210006100117260010600178300001000284490000700294520110800301653001401409653001401423653003201437653001601469653001601485653001701501653002001518100002201538700002201560700002201582700002001604856009501624       2015                        eng d  a0965-174800aCathepsins of lepidopteran insects: aspects and prospects0 aCathepsins of lepidopteran insects aspects and prospects  aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcSEP  a51-590 v643 a<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>10aApoptosis10aCathepsin10aCysteine/aspartate protease10aDevelopment10aLepidoptera10aPest control10aStress response1 aSaikhedkar, Nidhi1 aSummanwar, Aarohi1 aJoshi, Rakesh, S.1 aGiri, Ashok, P.  uhttps://library.ncl.res.in/content/cathepsins-lepidopteran-insects-aspects-and-prospects-002420nas a2200265   4500008004100000245011300041210006900154260000800223300000600231490000700237520156200244653001401806653003101820653001401851653001301865653001301878653001101891653002401902100001901926700001901945700002601964700002201990700001902012856012302031       2021                        eng d00aRepurposing the McoTI-II rigid molecular scaffold in to inhibitor of `papain superfamily' cysteine proteases0 aRepurposing the McoTIII rigid molecular scaffold in to inhibitor  cJAN  a70 v143 a<p>Clan C1A or `papain superfamily' 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>
10aCathepsin10aClan CA cysteine proteases10acyclotide10acystatin10aMcoTI-II10apapain10aprotein engineering1 aMishra, Manasi1 aSingh, Vigyasa1 aTellis, Meenakshi, B.1 aJoshi, Rakesh, S.1 aSingh, Shailja  uhttps://library.ncl.res.in/content/repurposing-mcoti-ii-rigid-molecular-scaffold-inhibitor-papain-superfamily-cysteine