No abstract

Protein-protein interactions studies can greatly increase the amount of structural and functional information pertaining to biologically active molecules and processes. The information obtained from such studies can lead to design and application of new modification in order to obtain a desired bioactivity. Many application packages and servers performing docking, such as HEX, DOT, AUTODOCK, and ZDOCK are now available for predicting the lowest free energy state of a protein complex. In this study, we have focused on cyclin-dependent kinase 4 (Cdk4), a key molecule in the regulation of cell cycle progression at the G1-S phase restriction point and p16INK4a, a tumor suppressor which inhibits Cdk4 activity. Truncated structures were created to find the more critical regions of p16 for interaction. The tertiary structures were determined by ProSAL, GENO3D Web Server. We evaluated their interactions with Cdk4 using two docking systems, HEX 4.5 and DOT 1. Calculations were performed on a high-speed computer. Minimizations and visualizations were carried out by PdbViewer 3.7. Considering shape and shape/electrostatic total energy, structures containing ANK II, III and IV motifs that lack the N-terminal region of the full length p16 molecule showed the best fit complexes among the p16 truncated forms. The free energies were compatible with that of p16 full length original form, the full length. It seems that the N-terminal of the molecule is not crucial for the interaction since the truncated structure containing only this region did not show a good total energy.

Development of sexually transmitted infections (STI) has existed in human societies along the history of mankind. It is still an important issue and research to diagnose and treat this group of diseases is growing. Due to the microbial antibiotic resistance to classical antibiotics, finding new antimicrobial compounds is essential. Aantimicrobial peptides (AMPs) are of the most important of these compounds. AMPs ususally show a broad spectrum of activities. Defensins, secretory leukocyte protease inhibitors (SLPI), calprotectin, lysozyme, lactoferrin and elafin are familes of antimicrobial peptides that are involved in vaginal innate immunity. Some of AMPs such as LL-37, magainin 2 and nisin A have dual spermicide and microbicide effects. LL-37 is the most suitable peptide for this purpose with both spermicide/microbicide properties. LL-37 formulated gel administered into the vagina would exert microbicidal action on uropathogenic microbes.However, LL-37 is a long peptide and its synthesis is very expensive, hence the shortest truncated active form of LL-37 peptide or its mimetic, has to be designed. Also, setting up production method for recombinant LL-37 is necessary. In addition in silico methods can help this process and modification of AMPs. So, the proper formulation of the LL-37 as a vaginal spermicide/microbicide can play a role in the health of women.

No abstract

HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

No abstract

Manipulating the cytoplasmic folding environment by increasing the intracellular concentration of folding modulators, such as chaperone molecules, causes the convenient production of heterologous proteins. Wrong selection of chaperones will negatively affect the host cells physiology and the production of heterologous proteins. Due to this reason, type and combination of chaperone molecules are crucial to produce more soluble and active form of target protein. In the current study, the cooverproduction of five different combinations of 6 chaperones, comprising "DnaK/DnaJ/GrpE/GroES/ GroEL", "GroES/GroEL", "DnaK/DnaJ/GrpE", "GroES/GroEL/TF" and "TF" along with recombinant human basic fibroblast growth factor (rhbFGF) were studied. As a result, we proved that none of these combinations was able to completely prevent the formation of inclusion bodies, but co-overexpression of the bacterial chaperone system TF along with rhbFGF could significantly enhance the yield of soluble protein. Recombinant soluble hbFGF that co-expressed with TF was then purified from the cells and was found to be identical to the active rhbFGF expressed alone with respect to size and spectral properties.