Life Sciences & Biotechnology
Title : | Identification of novel inhibitors for lysine/Dap pathway in Mycobacterium tuberculosis |
Area of research : | Life Sciences & Biotechnology, Computer Sciences and Information Technology |
Focus area : | Bioinformatics |
Principal Investigator : | Dr Ashwani Kumar Sharma, Associate Professor, Indian Institute of Technology (IIT), Roorkee |
Timeline Start Year : | 2012 |
Timeline End Year : | 2015 |
Contact info : | aksbsfbs@iitr.ernet.in; paroyfbs@iitr.ernet.in |
Details
Executive Summary : | The 2S albumin family proteins are multifunctional proteins and have gained importance due to the biotechnologically exploitable properties. Many proteins of the family have been shown to possess more than one function which may include translational inhibitory, antimicrobial, and serine proteinase inhibitory activities. The purification, characterization and cloning of a novel multifunctional ~12 kDa heterodimeric proteins belonging to 2S albumin family from two different plant families Euphorbeace (Putranjiva roxburghii ) and Curbitaceae (Cucurbita maxima) was carried out. Pumpkin 2S albumin exhibited anticancer, DNase and antifungal activities apart from RNase and cell-free translational inhibitory activities reported earlier. The protein exhibited a strong anti-cancer activity toward breast cancer (MCF-7), ovarian teratocarcinoma (PA-1), prostate cancer (PC3 and DU-145) and hepatocellular carcinoma (HepG2) cell lines. Acridine orange staining and DNA fragmentation studies indicated that cytotoxic effect of pumpkin 2S albumin is mediated through induction of apoptosis. Pumpkin 2S albumin showed DNase activity against both supercoiled and linear DNA and exerted antifungal activity. Secondary structure analysis by CD showed tha tit is highly stable up to 90°C and retains its alpha helical structure. Putranjiva roxburghii 2S albumin (putrin) exhibited both RNase and DNase activities and exerted antifungal activity but possessed relatively weak translation-inhibitory activity in cell-free system. Circular dichroism studies demonstrated the helical nature and conformational stability of protein at increasing temperatures. The cloning and sequence analysis revealed a 414 bp open reading frame encoding a preproprotein of 137 amino acid residues. The amino acid sequence comparisons and phylogenetic analysis of putrin showed significant homology to 2S seed storage family proteins. These results demonstrated that both putrin and pumpkin 2S albumin are multifunctional proteins with a range of pharmacologically important functions which can have potential therapeutic value and pumpkin 2S albumin could be developed as a potential antitumor agent. |
Co-PI: | Dr. Partha Roy, Associate Professor, Indian Institute of Technology (IIT), Roorkee |
Publications : | 2 |
PhD Produced : | 1 |
Organizations involved
