Current Protein and Peptide Science - Volume 18, Issue 3, 2017

The α/β hydrolase fold superfamily is an ancient and widely diversified group of primarily hydrolytic enzymes. In this review, the adaptations of these proteins to the pathogenic lifestyle of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, are examined. Of the 105 α/β hydrolases identified in Mtb, many are associated with lipid metabolism, particularly in the biosynthesis and maintenance of the Mtb’s unique cell envelope, as well in the large number of extracellular lipases that are likely responsible for degradation of host lipid material. α/β hydrolase fold proteins are also involved in the evasion and modulation of the immune response, detoxification and metabolic adaptations, including growth, response to acidification of the intracellular environment and dormancy. A striking feature of Mtb’s α/β hydrolases is their diversification into virulence-associated niches. It is clear that the α/β hydrolase fold family has made a significant contribution to Mtb’s remarkable success as a pathogen.

Since the first and the last residues of a protein have peculiar properties, unique amongst all residues, they have been analyzed repeatedly during the last decades. In this brief review, I try to summarize, besides the biochemical roles, the five features that have attracted most attention: (i) the Euclidean distance between the N- and C-termini and its relevance to protein folding, (ii) the reason why the termini are solvent exposed, (iii) the backbone conformation of the termini, (iv) the amino acid composition of the termini, and (v) the role of the termini in protein crystallization. Each of these five issues, which deserve attention nowadays thanks to the availability of massive amounts of data, is accompanied by my personal outlook of the research in the field.

Therapeutic proteins are engineered proteins produced in the laboratory for pharmaceutical use. With the advent of recombinant DNA technology, the proteins can be generated in specific host cells under defined conditions. In the process of production of genetically engineered animals, the gene of interest can be added at a single cell stage to produce a cloned animal from genetically engineered cells. Several recombinant cytokines, clotting factors etc have been licensed and are currently being utilized for the treatment of cancer, infectious diseases, hemophilia, anemia, multiple sclerosis, and hepatitis B/C. Therapeutic proteins that are useful for human are successfully produced in poultry as well as in livestock animals. However, the fastest growing class of therapeutic proteins are antibodies especially monoclonal antibodies (mAb), the most important class of therapeutic protein with the potential to generate significant revolution in terms of clinical success rate. Here, we review the most recent clinical advances in the field of emerging and existing therapeutic proteins.

Site-directed mutagenesis allows elucidation of the basic principles of the porin-driven membrane permeability and opens the possibility for the modulation of functional states of porin channels. The review is aimed to show the advantages of using mutant and chemically modified porins for obtaining detailed information about molecular mechanisms that underlie the non-specific transmembrane diffusion. We summarized data regarding the effects of the point substitutions and the external loop deletions on electrophysiological properties of general porins. The influence of charges inside the pore eyelet and the roles of external loops in ion conductance, ion selectivity, and voltage gating were described.

The morbidity and mortality after solid organ transplantation leads to poor outcomes in the long-term graft survival. There are many sources increasing bad outcomes within the post-transplant period reducing the quality of recipient´s life, such as rejection episodes, opportunistic infections as well as immunosuppression related morbidity. A complete understanding on the immune system responses against the allo-graft remains unknown. Recently, some pro-inflammatory cytokines, such as IFN-γ and IL-17, as well as IL-2, have been proposed as surrogate biomarkers able to predict the appearance of clinical event episodes. In this review we summarize the latest findings regarding the immune function monitoring in solid organ transplantation as well as the most common techniques (ELISPOT, ELISA and Flow Cytometry) that have been widely used across different clinical laboratories.

RNA-binding proteins play critical roles in the regulation of gene expression. Among several families of RNA-binding proteins, PUF (Pumilio and FBF) proteins have been the subject of extensive investigations, as they can bind RNA in a sequence-specific manner and they are evolutionarily conserved among a wide range of organisms. The outstanding feature of these proteins is a highly conserved RNA-binding domain, which is known as the Pumilio-homology domain (PUM-HD) that mostly consists of eight tandem repeats. Each repeat recognizes an RNA base with a simple three-letter code that can be programmed in order to change the sequence-specificity of the protein. Using this tailored architecture, researchers have been able to change the specificity of the PUM-HD and target desired transcripts in the cell, even in subcellular compartments. The potential applications of this versatile tool in molecular cell biology seem unbounded and the use of these factors in pharmaceutics might be an interesting field of study in near future.

Antifreeze proteins are ice-binding or ice-structuring proteins that prevent water from freezing by adsorbing to the ice surface and stopping the growth of minute ice crystals to large crystals in a non-colligative manner. The antifreeze proteins are found in species like fish, arthropods, plants, algae, fungi, yeasts and bacteria. The diversity, distribution and classification of antifreeze proteins were highlighted in this review. Antifreeze proteins help the organisms adapt to and survive in subzero temperature environments. The distribution of antifreeze proteins in different species appears to be the outcome of a combination of independent evolutionary events, probably the convergent evolution or horizontal gene transfer. Benefits can be derived from the frost resistance of these organisms. Their potential applications have been recognized in food processing, cryopreservation, cryosurgery, fishery and agricultural industries and anti-icing materials development. This review includes information on the current understanding of antifreeze proteins. A discussion on interactions and mechanisms involving ice recognition and adsorption was also included.

Endophytic peptides have been considered as potential therapeutic sources of future antibiotics because of their broad-spectrum activities and different mechanisms of action compared to the conventional antibiotics. The world human population is increasingly facing different types of health issues. For instance, emerging wide array of the drug-resistant pathogens is a health concern. Research on bioactive agents and other natural products of microbes is essential to combat antimicrobial resistance. It is necessary to find new potential antibiotics to address this problem. The use of therapeutic plants in traditional medicine is well known. The medicinal plants contain endophytes which are repositories of bioactive compounds. The natural therapeutic agents produced by endophytes do have several potential applications in the field of pharmaceutical industry. Ecomycins, Pseudomycins, Munumbicins and Xiamycins are the antibacterial, antimycotic and antiplasmodial endophytic derived bioactive agents. Among these, some are having significant antiviral properties and inhibitory activity against plant and human bacterial pathogens. Therefore, to deal with emerging drug-resistant pathogens endophytic peptides could serve as a potential source of novel antibiotics. This review focuses on the peptides derived from plant endophytes, their biological and pharmaceutical applications, and their mechanisms of action.