Bioinformatic review of Dianthins to identify the most suitable RIP for the production of protein with biological properties
Bioinformatic review of Dianthins to identify the most suitable RIP for the production of protein with biological properties
Fatemeh Khakdan,1,*Mobina Toranjideh,2
1. Department of Biology, Farzanegan Campus, Semnan University 2. Department of Biology, Farzanegan Campus, Semnan University
Introduction: Despite the promising advances that have been made in various treatments such as chemotherapy, radiation therapy and surgery, the treatment of all types of this disease is considered a challenge today; therefore, with the advances in molecular knowledge, research to find effective and new anti-cancer agents with high selectivity and specificity are of great importance. For this purpose, people have focused their research on natural herbal products or medicines taken from natural sources. Plant toxins are one of the important topics for the development of new cytotoxic drugs against cancer, and currently many plant toxins have been identified, including ribosome inactivating proteins, which belong to a group of enzymes known in plants, algae are fungi and bacteria, he pointed out. These proteins (RIPs) are divided into two types, and the Dianthin enzymes we are discussing are a toxic plant protein belonging to the family of ribosome inactivating proteins (RIPs) type 1
Methods: Comparative and bioinformatics analyzes were investigated.
Results: In the following investigations, the results of the analysis of the Dianthin coding sequence were obtained as follows: the full length of the mRNA is 1153 base pairs, the amino acid sequence is 293, and the C-terminal region of the sequence contains sugars such as mannose, glucose, and glucosamine. Further analysis and analysis of the coding sequence of Dianthin allowed us to obtain its physicochemical properties such as molecular weight equal to 32 kilodaltons, isoelectric point 8.92, aliphatic index: 91.23, GRAVY index of hydrophobicity and the presence or absence of a disulfide bond, as well as the presence of a cysteine amino acid in the position 243 and peptidochloroplasty signal helped. After receiving this information, we studied the structure of this protein, and the results of different components in its second structure, such as 40.96% random coil, 36.86% a-helix, It showed 18.09% extended strand and 4.10% B turn; Also, in its third structure, the presence of the amino acid tyrosine in the active site of the enzyme, as well as the presence of positively and negatively charged amino acids, as well as the catalytic pocket containing glutamate and arginine amino acids, were visible. In further investigations, the functional analysis of Dianthin was not neglected and the exploration of amino acid sequence motifs added the presence of the Shiga-Ricin conserved sequence at amino acid position 211-195 to our findings; also, studies were conducted on the homology of Dianthin sequence with various RIPs. It was found that the detailed results are available in the description, which we refer to a part of it here; Dianthin-30 is very similar to saporin-S3 and saporin-S6, two RIPs that are often used to design targeted toxins for tumor therapy and have already been tested in some clinical trials.
Conclusion: Finally, through investigations and during the course of the study, we found that first, Diantin-30 and 32 are the best Diantin enzymes in the last decade; Secondly, as we said before, Dianthin is a very active enzyme from the type 1 RIPs family, which does not have a second cellular connection, so it shows low cytotoxicity; This feature makes Dianthin an attractive candidate for targeted tumor therapy. Supplementary description of the article provides an overview of the discovery history of Dianthin and elucidates its structure, function and role in targeted toxins in more detail. It also discusses the option of increasing the efficacy of Dianthin based on the non-degradation of targeted Dianthin in lysosomes and subsequently increasing cytotoxicity for the target cell by endosomal escape enhancers.